Antisense lncRNAs in Hepatocellular Carcinoma: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Peter Tang and Version 3 by Nicola MOSCA.

Transcriptome complexity is emerging as an unprecedented and fascinating domain, especially by high-throughput sequencing technologies that have unveiled a plethora of new non-coding RNA biotypes. Several sense–antisense transcript pairs have been recently annotated, especially from mammalian genomes, and an understanding of their evolutionary sense and functional role for human health and diseases is only beginning. Antisense long non-coding RNAs ((lncRNAs) dysregulation is significantly involved in hepatocarcinogenesis, where they can act as oncogenes or oncosuppressors, thus playing a key role in tumor onset, progression, and chemoradiotherapy response. Mechanistically, antisense lncRNAs regulate gene expression by exploiting various molecular mechanisms shared with other ncRNA molecules, and exploit special mechanisms on their corresponding sense gene due to sequence complementarity, thus exerting epigenetic, transcriptional, post-transcriptional, and translational controls.

  • non-coding RNA
  • antisense lncRNA
  • HCC
  • ceRNET

1. Introduction

As the result of pervasive transcription of the mammalian genome, non-coding RNAs (ncRNAs) represent the majority of the transcriptome. High-throughput sequencing technologies unveiled an unprecedent and fascinating picture of transcriptome complexity, where less than 2% of transcription encodes proteins, and a plethora of ncRNA biotypes are found, in addition to the well-known ribosomal RNAs [1]. The finely regulated expression pattern of ncRNAs, further restricted to specific cell types in comparison to coding RNAs, their role in various physiological processes, and the finding of their dysregulation and involvement in pathological conditions have led to a drastic change in the view of ncRNA world: ncRNAs are no longer considered “evolutionary junk” or “transcriptional noise”, but a valuable resource for greater eukaryote complexity, with molecular mechanisms only beginning to be understood [2][3].
Based on their length, ncRNA molecules can be broadly classified into small or short ncRNAs (from few to 200nt) and long ncRNAs ((lncRNAs) longer than 200nt, with a size up to several kilobases (up to 100 kb)) [4].
Short ncRNAs comprise tRNA (transfer RNA), engaged in translation of mRNA; snRNA (small nuclear RNA), involved in splicing; snoRNA (small nucleolar RNA), involved in ribosomal RNA modification; piRNA (Piwi-interacting RNA), mainly implicated in transposon repression; microRNAs (miRNAs), the most studied group of small ncRNAs, acting as post-transcriptional regulators of gene expression (Figure 1). miRNAs work by driving multiprotein complexes on complementary sequences of target transcripts, thus affecting their translation and/or stability [5]. One miRNA can bind various transcripts, and vice versa one transcript can be targeted by different miRNAs, giving rise to complex regulatory networks controlling more than 30% of protein-coding genes, thus playing key roles in almost all physiological pathways and in the pathogenesis of several diseases [6][7][8].
Figure 1. Graphic representation of RNA biotypes’ classification in the transcriptome space. ncRNAs represent the majority of the transcriptome. In addition to the well-known ribosomal RNAs, they can be broadly classified into short and long non-coding RNAs; they can be further functionally categorized as indicated. lncRNAs, the largest class of ncRNAs in the mammalian genome, can be classified into subclasses depending on their genomic locations, origins, and transcription direction. Figures created with BioRender.com.
LncRNAs, the largest class of ncRNAs in the mammalian genome, can be further classified into subclasses, depending on their genomic locations, origins, and transcription directions (Figure 1): long intergenic ncRNAs (lincRNAs) transcribed from intergenic regions that do not overlap any other gene and have their own regulatory elements; sense lncRNAs, transcribed in the same direction as a coding gene, overlapping one or more exons or embedded in one of the introns without touching any exons (intronic lncRNAs); antisense lncRNAs, transcribed as an antisense strand compared to an overlapping known gene; bidirectional (or divergent) lncRNAs, deriving from promoters with bidirectional activity; pseudogenes, a version of coding genes that lost their protein-coding ability due to mutations; eRNAs (enhancer RNAs), arising from enhancers endowed with an enhancer-like function; circRNAs (circular RNAs), deriving from backsplicing events of protein-coding transcripts that form covalently closed continuous loops [2][4][9][10]. LncRNAs are emerging as key gene expression regulators due to their interaction with DNA, other RNA molecules, and proteins, as detailed in the next paragraph.
The specific name of antisense lncRNAs is derived from their sense gene, with the addition of “-AS”; they can be further categorized according to their localization with respect to sense transcripts, i.e., tail to tail (sense and antisense transcripts overlapping in the 3′ region), internal (antisense lncRNA covering the sense transcript), and head to head (sense and antisense transcripts overlapping the 5′ region) [11].
Sense–antisense gene pairs have been found in a significant proportion in the genome/transcriptome of different species, from prokaryotes to mammals (a higher percentage has been found in mammals); furthermore, sense–antisense gene pairs are generally organized into one coding and one non-coding transcript [12][13][14]. Intriguingly, evolutionary conservation of sense–antisense gene pairs has been reported as low, even between closely related mammals; in particular, only 25% of human pairs have both genomic sequence and gene structure conservation in mice [15]. This evidence, along with the poor evolutionary conservation of lncRNAs’ sequence and their role in gene regulation, lead us to speculate that many interspecies differences could rely on the regulation of protein-coding genes, significantly conserved throughout evolution, by non-conserved antisense lncRNAs. In this regard, it has been inferred that human sense–antisense gene loci may be enriched for primate-specific regulatory functions, and antisense lncRNAs could represent the “linchpins of interspecies distinctions” contributing to evolutionary lineage-specific regulatory outcomes and complexity [15].
It is becoming increasingly clear that antisense lncRNAs play key roles, not only in physiological states, but also in pathological conditions, especially cancer. They can contribute to the onset and progression of different types of tumors, acting as oncogenes, oncosuppressors, or both, depending on the type of cancer. lncRNAs have also been implicated in chemotherapy and radiation therapy resistance.
Antisense lncRNAs are also emerging as novel players in hepatocellular carcinoma (HCC); in particular, one study found that they represent 16% of the newly assembled lncRNAs from HCC patients [16]. HCC is one of the most common aggressive human malignancies. HCC ranks third for cancer-related death and is the fifth most common solid tumor worldwide [17]. Viral hepatitis, metabolic syndrome, alcohol abuse, exposure to carcinogenic agents, and genetic diseases such as Wilson’s disease and hemochromatosis can cause chronic liver diseases, resulting in more than 80% of human HCCs [18]. In addition to the well-known role of protein-driven processes, functional studies have demonstrated the active involvement of ncRNAs in the regulation of key pathways acting in hepatocarcinogenesis [19][20].

2. Biogenesis and Functioning of Antisense lncRNAs

Antisense lncRNAs and, generally, lncRNA biogenesis, share various features with coding RNAs and precursor transcripts of miRNAs: they are transcribed, generally, by RNA polymerase II, subjected to 5′-capping, 3′-polyadenylation, and splicing, since they are mainly composed of two exons [2]. In contrast with mRNAs that move to the cytoplasm for translation, antisense lncRNAs can be retained in the nucleus. Similarly to coding RNAs, but even more distinctly, lncRNAs exhibit highly specific cell lineage and restricted spatiotemporal and tissue type expression patterns, although they are detected in lower amounts [3]. It is still challenging to assign a mechanism/role to the increasing numbers of annotated antisense lncRNAs, due to their lower amounts and poor evolutionary conservation when compared to coding RNAs. In this regard, it should be noted that conservation may be found in secondary structures rather than in sequences; in fact, a crucial feature of lncRNAs is the ability to form thermodynamically stable structures, a structural versatility enabling them to bind to DNA, other RNA molecules, and proteins [21][22]. In addition, an RNA molecule comprising 100nt can capture more than 5 proteins simultaneously, making RNA molecules a more cost-effective scaffold for protein interaction, in comparison to proteins themselves, with well-known modules/motifs dedicated to interactions [23]. In the nucleus and cytoplasm, antisense lncRNAs exploit all the mechanisms of gene regulation known for other lncRNA biotypes. However, antisense lncRNAs can also reroute these mechanisms onto their sense genes. In addition, due to sequence complementary, antisense lncRNAs can play a special role regarding sense genes (Figure 2). As a consequence, an efficient manner to obtain clues regarding the main mechanism of action of antisense lncRNAs is to detect their prevailing subcellular localization while taking into consideration a possible shuttling between different compartments under specific physiological or pathological conditions. Then, it is possible to speculate that some of the activities performed in that compartment may involve the regulatory contribution of antisense lncRNAs.
Figure 2. Molecular mechanisms exploited by antisense lncRNAs for gene expression regulation and involved in HCC. Antisense lncRNAs can interact with DNA, RNA, and proteins, thus sharing the mechanisms of gene regulation known for other lncRNA biotypes, and also rerouting them onto their sense genes. Here, the possible mechanisms are represented as compartmentalized between the nucleus and the cytoplasm, with different sublevels (a–g) to emphasize the idea that the subcellular localization of a newly annotated antisense lncRNA can provide clues about its prevailing mechanism of action. However, a possible shuttling of antisense lncRNA should be considered in diverse physiological and/or pathological contexts. Many of the illustrated mechanisms are involved in the onset and progression of HCC, as detailed in the text. Figures created with BioRender.com.
In the nucleus, interaction with DNA, chromatin-modifying complexes, histone-modifying enzymes, and/or various transcriptional regulators determines antisense lncRNAs function as epigenetic and transcriptional regulators (Figure 2a–c). In particular, antisense lncRNAs can recruit DNA methyltransferases to promoters, thus actively contributing to DNA methylation pattern impacting the expression of a large number of oncogenes or tumor suppressors [24][25]. Antisense lncRNAs can also recruit demethylation enzymatic activities to promoters —as has been demonstrated— by RIP (RNA immunoprecipitation) and RNA pull-down experiments—for ZNF667-AS1, able to interact and recruit TET1 to the target gene ZNF667 and E-cadherin to hydrolyze 5′-methylcytosine to 5′-hydroxymerhylcytosine and activate its expression [24][26]. Of note, specific DNA methylation signatures are associated with the HCC stage and patient survival [27][28]. Specific antisense lncRNAs can also interact and recruit chromatin-remodeling complexes and histone-modifying enzymes, such as histone methyltransferase and histone acetyltransferases, that cannot exert their role independently due to a lack of a DNA-binding domain, thus modulating chromatin structure influencing gene expression [11][29][30]. At the transcriptional level, antisense lncRNAs can recruit transcription factors required for promoting or repressing gene expression [31][32]. Although less frequently reported, lncRNAs can also directly bind to genomic DNA to regulate gene expression. An example of this is represented by VIM-AS1 that forms a hybrid DNA:RNA structure, known as R-loop, around the promoter of its head-to-head sense gene VIM, thus triggering an open chromatin structure that favors NF-kB binding and VIM transcription [33]. Another manner of direct lncRNA-DNA interaction is the formation of RNA-DNA triplex, impacting transcriptional induction [34]. Finally, in the nucleus, lncRNAs can also regulate splicing by interacting with splicing factors [20]. In the cytoplasm, by binding proteins and RNA molecules, lncRNAs can regulate gene expression at the post-transcriptional level by sponging miRNAs, regulating mRNA translation and degradation; short open reading frames hidden in the lncRNA sequence could even serve as templates for the synthesis of so-called “micropeptides” up to 100 amino acids long [4][35][36] (Figure 2d–g). Currently, many studies are being published on miRNAs sponging activity of antisense lncRNA and ceRNA activity (competing endogenous RNA): the lncRNA can bind a miRNA and, titrating its availability, can endogenously compete with the other miRNA targets, coding or non-coding RNAs, that are resultingly upregulated [37][38]. In this scenario, all RNA biotypes can modulate each other and design regulatory networks (ceRNET, competing endogenous RNA network) governing different pathways, and whose unbalancing can drive carcinogenesis [39][40]. Even at the post-translational level, antisense lncRNAs can exert control of gene expression by binding and modulating the stability of specific proteins, e.g., protecting from or prompting their ubiquitin-proteosome degradation, and modifying their phosphorylation status, or controlling their localization [11][41]. Finally, sequence complementary allows antisense lncRNAs to have a specific effect on their sense gene. In fact, at the post-transcriptional level, antisense lncRNAs can bind their sense transcript, generating an RNA duplex and affecting the stability of the sense transcript via an RNA interference mechanism; probably the best-known example of this is represented by the pair XIST and TSIX (XIST spelled in reverse order) involved in the X chromosome inactivation, but other examples have been subsequently reported [42][43][44] (Figure 2d). An opposite effect to RNAi can also be observed, due to the stabilization of cognate RNA by interaction with antisense lncRNA [37][38][45]. The above mechanisms have been distilled from many studies, detailed in the next section as related to HCC.

3. Antisense lncRNAs Involved in HCC

Antisense lncRNAs are increasingly recognized as mediators of human cancers [11] and, depending on the context, they can act as either oncogenes or tumor suppressors. In the liver, a number of antisense lncRNAs are described as deregulated, thus playing a crucial role in the onset and progression of HCC [16]. In particular, by searching “(antisense lncRNA) AND (HCC)” throughout PubMed, more than 200 articles were retrieved; they were then analyzed and articles concerning antisense lncRNAs were grouped as detailed below. This analysis was also based on information retrieved from https://lncipedia.org (accessed on 3 April 2023) [46]. An extended list of antisense lncRNAs, their dysregulation, and their molecular functions in HCC is provided in Table 1.
Table 1. Antisense lncRNAs acting as oncogenes or tumor suppressors in HCC.

Antisense lncRNA

Role

Effect

Molecular Mechanism

Reference

AIRN

Oncogene

Promotes proliferation and inhibits apoptosis

Inhibits CUL4A-mediated ubiquitination of STAT1

[47]

ALKBH3-AS1

Oncogene

Promotes cell invasion and proliferation

Enhances ALKBH3 mRNA stability

[48]

ANRIL

Oncogene

Associated with clinical outcomes; promotes proliferation, migration and invasion; promotes tumor growth and metastasis in vivo; enhances mitochondrial function

Silences epigenetically Kruppel-like factor 2 (KLF2) by binding to PRC2 sponges let-7c-5p to upregulate NAP1L1, thus activating AKT/mTOR pathway; sponges miR-191, inactivating NF-κB and Wnt/β-catenin pathways; sponges miR-153-5p to upregulate ARHGAP18 and activate MEK/ERK signaling;

sponges miR-199a-5p to upregulate ARL2; sponges miR-122-5p

[49][50][51][52][53][54]

BACE1-AS

Oncogene

Promotes cell cycle progression, migration, and invasion

Sponges miR-214-3p to upregulate APLN expression

[55]

BAIAP2-AS1

Oncogene

Promotes proliferation and metastasis

Sponges miR-361-3p to release SOX4

[56]

BSG-AS1

Oncogene

Correlates to hypoxia; promotes proliferation and migration

Enhances the stability of BSG mRNA

[57]

DARS-A1

Oncogene

Correlates with poor prognosis; promotes proliferation, cell invasion, and EMT

Sponges miR-3200-5p to upregulate CKAP2 and activate the FAK/ERK pathway

[58]

DDX11-AS1

Oncogene

Promotes proliferation, migration, invasion and glucose metabolism

Sponges miR-195-5p to upregulate MACC1 expression

[59]

DLG1-AS1

Oncogene

Promotes proliferation, migration, and invasion in HCC and tumor growth in vivo

Induced by MYC; sponges miR-497-5p to upregulare SSRP1

[60]

DLGAP1-AS1

Oncogene

Promotes proliferation

Sponges miR-486-5p to upregulate H3F3B

[61]

DNAJC3-AS1

Oncogene

Correlates with prognosis of patients; promotes proliferation

Suppresses miR-27b maturation

[62]

DLX6-AS1

Oncogene

Promotes cell viability, invasion, and migration

Sponges miR-513c to upregulate Cul4A, thus repressing ANXA10 degradation; sponges miR-424-5p to upregulate WEE1

[63][64]

FAM83H-AS1

Oncogene

Associated with tumor prognosis; promotes proliferation, migration, and invasion

Inhibits the Wnt/β-catenin pathway by reducing β-catenin and WNT1 expression

[65]

FGFR3-AS1

Oncogene

Promotes proliferation, migration, and invasion; promotes tumor growth in vivo

Activates the PI3K/AKT pathway

[66]

FOXP4-AS1

Oncogene

Associated with poor survival, promotes tumor growth in vivo

Recruits EZH2 to the promoter region of ZC3H12D to mediate H3K27me3 methylation, thus inhibiting ZC3H12D expression

[29]

GATA3-AS1

Oncogene

Promotes cell proliferation and metastasis

Suppresses PTEN, CDKN1A, and TP53

[67]

GPC3-AS1

Oncogene

Indicates poor prognosis; proliferation and migration; Promotes xenograft tumor growth in nude mice

Recruits PCAF to the GPC3 gene body region, upregulating GPC3 transcription

[68]

HOTAIR

Oncogene

Promotes proliferation, migration, invasion, and tumor growth in vivo; regulates the G1/S phase transition; regulates glycolyis; associated with poor survival rates

Increases ATG3 and ATG7 expression; inhibits RBM38; activates Wnt/β-catenin pathway, increases CCND1 expression and STAT3 signaling; binds STAT3 andP300 to upregulate FUT8 and MUC1; upregulates GLUT1, upregulating mTOR; sponges miR-130a-3p to upregulate HIF1A regulated by FOXC1; sponges miR-1; sponges miR-214-3p to upregulate FLOT1

[32][69][70][71][72][73][74][75][76]

HOXA11-AS1

Oncogene

Promotes proliferation, invasion, and self-renewal

Suppresses the transcription of HOXA11 by recruiting DNMT1 to the promoter activating Wnt/βcatenin pathway

[25]

HOXA-AS2

Oncogene

Promotes cell migration and invasion by inducing EMT

Sponges miR-520c-3p to upregulate GPC3

[77]

HOXD-AS1

Oncogene

Promotes proliferation and invasion; regulates cell cycle progression

Sponges miR-miR-326 to upregulate SLC27A4, induces MEK/ERK signaling pathway

[78][79]

KCNQ1OT1

Oncogene

Correlates with liver cirrhosis, an advanced TNM stage, and a large tumor size; promotes proliferation and tumor growth in vivo

Sponges miR-504 to regulate GSK3β/β-catenin/Bcl-2 signaling pathway

[80]

KTN1-AS1

Oncogene

Associated with poor survival, promotes proliferation

Sponges miR-23c to upregulate ERBB2IP

[81]

LASP1-AS

Oncogene

Associated with poor prognosis, enhances proliferation and migration

Upregulates LASP1

[82]

LEF1-AS1

Oncogene

Promotes proliferation, invasion, angiogenesis, and tumor growth in vivo

Sponges miR-136-5p to regulate WNK1 espression, recruits CEBPB to promote CDCA7/EZH2 expression

[30][83]

LOXL1-AS1

Oncogene

Promotes proliferation, migration, and invasion

Sponges miR-3614-5p to upregulate YY1

[84]

MACC1-AS

Oncogene

Increases stemness; promotes cell proliferation, EMT, and invasion

Sponges miR-145 to regulate Nanog, Oct4, and Sox9; regulates PAX8

[85][86]

MAFG-AS1

Oncogene

Promotes proliferation, invasion, and migration

Sponges miR-6852

[87]

MAPKAPK5-AS1

Oncogene

Associated with poor clinical features and prognosis, promotes growth and metastasis

Sponges miR-154-5p to upregulate PLAGL2, thus activating EGFR/AKT signaling and regulating HIFA

[88]

MCM3AP-AS1

Oncogene

Correlated with poor prognosis, promotes cell growth

Sponges miR-194-5p to upregulate FOXA1

[89]

MFI2-AS1

Oncogene

Promotes invasion and metastasis of HCC cells in vitro and vivo

Sponges miR-134 to upregulate FOXM1 expression

[90]

MKLN1-AS

Oncogene

Promotes proliferation, migration, invasion, and tumor growth in vivo; associated with poor prognosis

Sponges miR-22-3p to upregulate ETS proto-oncogene 1, sponges miR-654-3p to upregulate HDGF

[91][92]

MYLK-AS1

Oncogene

Associated with poor prognosis; promotes cell invasion, migration, proliferation, and angiogenesis

Sponges miR-424-5p to upregulate E2F7 and activate VEGFR2 signaling; increases EGFR, pEGFR, HER2 and RAF1 expression

[93][94]

NNT-AS1

Oncogene

Decreases CD4 lymphocyteinfiltration, promotes proliferation in vitro and tumor growth in vivo

Enhances TGF-β signaling pathway, sponges miR-363 to upregulate CDK6 expression

[95][96]

NPSR1-AS1

Oncogene

Promotes proliferation and glycolysis

Regulates MAPK/ERK pathway

[97]

NR2F1-AS1

Oncogene

Induces glycolysis under hypoxia and promotes migration

Sponges miR-140 to upregulate HK2

[98]

OTUD6B-AS1

Oncogene

Promotes proliferation and invasion

Sponges miR-664b3-p to induce GSKIP/Wnt/β-catenin signalling

[99]

PCNA-AS1

Oncogene

Promotes tumor growth in vitro and in vivo

Stabilizes PCNA transcripts

[100]

PITPNA-AS1

Oncogene

Promotes proliferation, migration, and EMT

Sponges miR-876-5p to upregulate WNT5A

[101]

PRKAG2-AS1

Oncogene

Associated with poor survival rates; promotes proliferation, migration, and invasion

Sponges miR-502-3p to upregulate BICD2

[102]

PRR34-AS1

Oncogene

Promotes proliferation migration, invasion, and EMT; enhances tumor growth in vivo

Sponges miR-296-5p to upregulate E2F2 and SOX12, activating Wnt/βcatenin pathway;

interacts with DDX3X to regulate the stability of Rab27a mRNA and promote the exosome secretion of VEGF and TGF-β;

sponges miR-498 to upregulate TOMM20 and ITGA6

[103][104][105]

RBM5-AS1

Oncogene

Promotes cell proliferation and invasion

Sponges miR-132/212 via recruiting PRC2 complex

[106]

RHPN1-AS1

Oncogene

Correlated with prognosis of patients; promotes proliferation and metastasis; associated with the occurrence of lymphatic metastasis and a higher level of serum AFP; correlated with poor survival

STAT1 induces overexpression of RHPN1-AS1, sponges miR-485 to upregulate CDCA5, sponges miR-596 to upregulate IGF2BP2

[107][108]

RNF185-AS1

Oncogene

Correlated with advanced TNM stage, distant metastasis and a poor survival rate; promotes proliferation, migration, and invasion

Sponges miR-221-5p to upregulate ITGB5

[109]

SBF2-AS1

Oncogene

Correlated with poor prognosis, promotes proliferation and tumor growth in vivo

Sponges miR-140-5p to upregulate TGFBR1 expression

[110]

SNAI3-AS1

Oncogene

Promotes proliferation and metastasis

Sponges miR-27-3p/34a-5p

[111]

SOX9-AS1

Oncogene

Promotes proliferation, migration, and invasion; Promotes tumor growth and metastasis in vivo

Sponges miR-5590-3p to upregulate SOX9, thus activating Wnt/b-catenin pathway

[112]

SPACA6P-AS

Oncogene

Promotes cell proliferation

Sponges miR-125a/Let7a to upregulate Lin28b, MMP11, SIRT7, Zbtb7a, Cyclin D1, CDC25B, HMGA2

[113]

ST8SIA6-AS1

Oncogene

Promotes proliferation, migration, and invasion

Sponges miR-338-3p to upregulate NONO expression, sponges miR-5195-3p to regulate HOXB6 expression

[114][115]

TMPO-AS1

Oncogene

Associated with poor prognosis, promotes proliferation and EMT

Sponges miR-126-3p to upregulate LRP6, inducing Wnt/β-catenin signalling; sponges miR-329-3p to upregulate FOXK1, inducing AKT/mTOR signaling pathway; sponges miR-320a to upregulate SERBP1

[116][117][118]

TP73-AS1

Oncogene

Correlated with poor prognosis, promotes proliferation

Sponges miR-200a to induce HMGB1/RAGE pathway

[119]

TRG-AS1

Oncogene

Promotes proliferation, migration, invasion, and EMT progress

Sponges miR-4500 to modulate BACH1

[120]

TRIM52-AS1

Oncogene

Promotes proliferation and EMT

Sponges miR-514a-5p to upregulate MRPS18A

[121]

TTN-AS1

Oncogene

Promotes proliferation, migration, and EMT

Sponges miR-139-5p to upregulate SPOCK1 expression

[122]

UNC5B-AS1

Oncogene

Promotes proliferation, migration, and EMT

Sponges miR-4306 to upregulate KDM2A expression

[123]

UPK1A-AS1

Oncogene

Correlated with poor prognosis, promotes proliferation and cell cycle progression

Interacts with EZH2; sponges miR-138-5p

[124]

USP2-AS1

Oncogene

Increases proliferation, migration, and invasion under hypoxia

Interacts with YBX1 to increase the protein translation of HIF1a under hypoxia

[125]

VPS9D1-AS1

Oncogene

Facilitates cell proliferation, migration, and stemness

Sponges miR-491-5p to upregulate SEC61A1

[126]

WEE2-AS1

Oncogene

Positively correlated to HBV infection; increases proliferation, migration, invasion, and cell cycle progression

Upregulates FERMT3 expression and activates PI3K/AKT/GSK3b signaling

[127]

ZEB1-AS1

Oncogene

Promotes proliferation and invasion, associated with bone metastasis

Sponges miR-229-3p to upregulate E2F1 expression, sponges miR-23c, sponges miR-302b to increase PI3K-AKT pathway activation and EGFR expression

[128][129][130]

ZEB2-AS1

Oncogene

Associated with large tumor volume, increased tumor-node-metastasis (TNM) stage, and positive lymph node metastasis; promotes proliferation, migration, invasion, and suppressed apoptosis

Sponges miR-582-5p to upregulate FOXC1

[131]

ZFAS1

Oncogene

Associated with worse prognosis and survival; promotes proliferation, migration, and invasion

Sponges miR-624 to upregulate MDK-mediated ERK/JNK/AKT signaling pathway

[132]

ZFPM2-AS1

Oncogene

Correlated with advanced TNM stage, distant metastasis, and a poor survival rate; promotes proliferation, migration, invasion, and tumor growth in vivo

Sponges miR-1226-3p to upregulate ITGB1, sponges miR-3065-5p activity to regulate XRCC4, sponges miR-139 to upregulate GDF10, sponges miR-653 to upregulate GOLM1

[133][134][135][136]

ZSCAN16-AS1

Oncogene

Correlated with poor clinical outcomes; promotes proliferation, migration, and invasion

Sponges miR-451a to increase ATF2 expression;

sponges miR-181c-5p to upregulate SPAG9, activating JNK

[137][138]

ADORA2A-AS1

Tumor suppressor

Inhibits proliferation, migration, and invasion; represses xenograft growth and metastasis in vivo

Competitively binds HuR decreasing FSCN1 transcript stability, thereby repressing the AKT pathway

[139]

CADM1-AS1

Tumor suppressor

Inhibits proliferation, migration, invasion, and tumor growth in vivo

Regulates the AKT/GSK-3β signaling pathway

[140]

F11-AS1

Tumor suppressor

Suppresses proliferation, migration, and invasion

Sponges miR-221-5p to upregulate NR1I3

[141]

HHIP-AS1

Tumor suppressor

Downregulation of HHIP-AS1 correlates with larger tumor size, metastasis, and advanced TNM stage; inhibits proliferation, migration, and invasion; induces apoptosis

Facilitates HHIP mRNA stability by promoting HuR binding to HHIP mRNA

[45]

HNF1A-AS1

Tumor suppressor

Suppresses proliferation, migration, and invasion; inhibits tumorigenesis and metastasis in vivo

Interacts and activates SHP-1

[142]

MAGI2-AS3

Tumor suppressor

Inhibits proliferation in vitro and tumor growth in vivo

Sponges miR-519c-3p to increase TXNIP, decreases RCGAP1 expression by facilitating histone demethylation of the RACGAP1 promoter by recruiting KDM1A

[143][144]

TMEM220-AS1

Tumor suppressor

Suppresses proliferation and invasion

Increases TMEM220 expression to regulate Wnt/β-catenin pathway

[145]

UCHLAS1

Tumor suppressor

Inhibits proliferation and migration

Enrichment analysis reveals that HRAS, BMP4, and CALM3 are hub genes of HCC, related to UCHLI-AS1

[146]

WT1-AS

Tumor suppressor

Promotes cell apoptosis

Inhibits JAK2/STAT3 and MAPK signaling, regulates WT1 by binding promoter region

[147]

WWOX-AS1

Tumor suppressor

Decreases cell proliferation, migration and EMT

Sponges miR-20b-5p to upregulate WWOX expression

[148]

References

  1. Dunham, I.; Kundaje, A.; Aldred, S.F.; Collins, P.J.; Davis, C.A.; Doyle, F.; Epstein, C.B.; Frietze, S.; Harrow, J.; Kaul, R.; et al. An Integrated Encyclopedia of DNA Elements in the Human Genome. Nature 2012, 489, 57–74.
  2. Derrien, T.; Johnson, R.; Bussotti, G.; Tanzer, A.; Djebali, S.; Tilgner, H.; Guernec, G.; Martin, D.; Merkel, A.; Knowles, D.G.; et al. The GENCODE v7 Catalog of Human Long Noncoding RNAs: Analysis of Their Gene Structure, Evolution, and Expression. Genome Res. 2012, 22, 1775–1789.
  3. Cabili, M.N.; Trapnell, C.; Goff, L.; Koziol, M.; Tazon-Vega, B.; Regev, A.; Rinn, J.L. Integrative Annotation of Human Large Intergenic Noncoding RNAs Reveals Global Properties and Specific Subclasses. Genes Dev. 2011, 25, 1915–1927.
  4. Beermann, J.; Piccoli, M.-T.; Viereck, J.; Thum, T. Non-Coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. Physiol. Rev. 2016, 96, 1297–1325.
  5. Bartel, D.P. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell 2004, 116, 281–297.
  6. Chang, T.-C.; Mendell, J.T. MicroRNAs in Vertebrate Physiology and Human Disease. Annu. Rev. Genom. Hum. Genet. 2007, 8, 215–239.
  7. Di Leva, G.; Garofalo, M.; Croce, C.M. MicroRNAs in Cancer. Annu. Rev. Pathol. Mech. Dis. 2014, 9, 287–314.
  8. Lewis, B.P.; Burge, C.B.; Bartel, D.P. Conserved Seed Pairing, Often Flanked by Adenosines, Indicates That Thousands of Human Genes Are MicroRNA Targets. Cell 2005, 120, 15–20.
  9. Alessio, E.; Bonadio, R.S.; Buson, L.; Chemello, F.; Cagnin, S. A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs. Int. J. Mol. Sci. 2020, 21, 302.
  10. Volders, P.-J.; Helsens, K.; Wang, X.; Menten, B.; Martens, L.; Gevaert, K.; Vandesompele, J.; Mestdagh, P. LNCipedia: A Database for Annotated Human LncRNA Transcript Sequences and Structures. Nucleic Acids Res. 2013, 41, D246–D251.
  11. Liu, B.; Xiang, W.; Liu, J.; Tang, J.; Wang, J.; Liu, B.; Long, Z.; Wang, L.; Yin, G.; Liu, J. The Regulatory Role of Antisense LncRNAs in Cancer. Cancer Cell Int. 2021, 21, 459.
  12. Engström, P.G.; Suzuki, H.; Ninomiya, N.; Akalin, A.; Sessa, L.; Lavorgna, G.; Brozzi, A.; Luzi, L.; Tan, S.L.; Yang, L.; et al. Complex Loci in Human and Mouse Genomes. PLoS Genet. 2006, 2, e47.
  13. Georg, J.; Hess, W.R. Cis-Antisense RNA, Another Level of Gene Regulation in Bacteria. Microbiol. Mol. Biol. Rev. 2011, 75, 286–300.
  14. Kutter, C.; Watt, S.; Stefflova, K.; Wilson, M.D.; Goncalves, A.; Ponting, C.P.; Odom, D.T.; Marques, A.C. Rapid Turnover of Long Noncoding RNAs and the Evolution of Gene Expression. PLoS Genet. 2012, 8, e1002841.
  15. Wood, E.; Chin-Inmanu, K.; Jia, H.; Lipovich, L. Sense-Antisense Gene Pairs: Sequence, Transcription, and Structure Are Not Conserved between Human and Mouse. Front. Genet. 2013, 4, 183.
  16. Yang, Y.; Chen, L.; Gu, J.; Zhang, H.; Yuan, J.; Lian, Q.; Lv, G.; Wang, S.; Wu, Y.; Yang, Y.-C.T.; et al. Recurrently Deregulated LncRNAs in Hepatocellular Carcinoma. Nat. Commun. 2017, 8, 14421.
  17. Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global Cancer Statistics. CA Cancer J. Clin. 2011, 61, 69–90.
  18. Shankaraiah, R.C.; Gramantieri, L.; Fornari, F.; Sabbioni, S.; Callegari, E.; Negrini, M. Animal Models of Hepatocellular Carcinoma Prevention. Cancers 2019, 11, 1792.
  19. Wong, C.-M.; Tsang, F.H.-C.; Ng, I.O.-L. Non-Coding RNAs in Hepatocellular Carcinoma: Molecular Functions and Pathological Implications. Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 137–151.
  20. Li, D.; Fan, X.; Li, Y.; Yang, J.; Lin, H. The Paradoxical Functions of Long Noncoding RNAs in Hepatocellular Carcinoma: Implications in Therapeutic Opportunities and Precision Medicine. Genes. Dis. 2022, 9, 358–369.
  21. Cruz, J.A.; Westhof, E. The Dynamic Landscapes of RNA Architecture. Cell 2009, 136, 604–609.
  22. Novikova, I.V.; Hennelly, S.P.; Tung, C.-S.; Sanbonmatsu, K.Y. Rise of the RNA Machines: Exploring the Structure of Long Non-Coding RNAs. J. Mol. Biol. 2013, 425, 3731–3746.
  23. Ribeiro, D.M.; Zanzoni, A.; Cipriano, A.; Delli Ponti, R.; Spinelli, L.; Ballarino, M.; Bozzoni, I.; Tartaglia, G.G.; Brun, C. Protein Complex Scaffolding Predicted as a Prevalent Function of Long Non-Coding RNAs. Nucleic Acids Res. 2018, 46, 917–928.
  24. Morris, K.V. Long Antisense Non-Coding RNAs Function to Direct Epigenetic Complexes That Regulate Transcription in Human Cells. Epigenetics 2009, 4, 296–301.
  25. Guo, J.-C.; Yang, Y.-J.; Zheng, J.-F.; Zhang, J.-Q.; Guo, M.; Yang, X.; Jiang, X.-L.; Xiang, L.; Li, Y.; Ping, H.; et al. Silencing of Long Noncoding RNA HOXA11-AS Inhibits the Wnt Signaling Pathway via the Upregulation of HOXA11 and Thereby Inhibits the Proliferation, Invasion, and Self-Renewal of Hepatocellular Carcinoma Stem Cells. Exp. Mol. Med. 2019, 51, 1–20.
  26. Dong, Z.; Li, S.; Wu, X.; Niu, Y.; Liang, X.; Yang, L.; Guo, Y.; Shen, S.; Liang, J.; Guo, W. Aberrant Hypermethylation-Mediated Downregulation of Antisense LncRNA ZNF667-AS1 and Its Sense Gene ZNF667 Correlate with Progression and Prognosis of Esophageal Squamous Cell Carcinoma. Cell Death Dis. 2019, 10, 930.
  27. Cheng, J.; Wei, D.; Ji, Y.; Chen, L.; Yang, L.; Li, G.; Wu, L.; Hou, T.; Xie, L.; Ding, G.; et al. Integrative Analysis of DNA Methylation and Gene Expression Reveals Hepatocellular Carcinoma-Specific Diagnostic Biomarkers. Genome Med. 2018, 10, 42.
  28. Mudbhary, R.; Hoshida, Y.; Chernyavskaya, Y.; Jacob, V.; Villanueva, A.; Fiel, M.I.; Chen, X.; Kojima, K.; Thung, S.; Bronson, R.T.; et al. UHRF1 Overexpression Drives DNA Hypomethylation and Hepatocellular Carcinoma. Cancer Cell 2014, 25, 196–209.
  29. Ye, J.; Fu, Y.; Wang, Z.; Yu, J. Long Non-Coding RNA FOXP4-AS1 Facilitates the Biological Functions of Hepatocellular Carcinoma Cells via Downregulating ZC3H12D by Mediating H3K27me3 through Recruitment of EZH2. Cell Biol. Toxicol. 2022, 38, 1047–1062.
  30. Gao, J.; Dai, C.; Yu, X.; Yin, X.-B.; Zhou, F. LncRNA LEF1-AS1 Silencing Diminishes EZH2 Expression to Delay Hepatocellular Carcinoma Development by Impairing CEBPB-Interaction with CDCA7. Cell Cycle 2020, 19, 870–883.
  31. Faghihi, M.A.; Wahlestedt, C. Regulatory Roles of Natural Antisense Transcripts. Nat. Rev. Mol. Cell Biol. 2009, 10, 637–643.
  32. Guo, Y.; Liu, B.; Huang, T.; Qi, X.; Li, S. HOTAIR Modulates Hepatocellular Carcinoma Progression by Activating FUT8/Core-Fucosylated Hsp90/MUC1/STAT3 Feedback Loop via JAK1/STAT3 Cascade. Dig. Liver Dis. 2023, 55, 113–122.
  33. Boque-Sastre, R.; Soler, M.; Oliveira-Mateos, C.; Portela, A.; Moutinho, C.; Sayols, S.; Villanueva, A.; Esteller, M.; Guil, S. Head-to-Head Antisense Transcription and R-Loop Formation Promotes Transcriptional Activation. Proc. Natl. Acad. Sci. USA 2015, 112, 5785–5790.
  34. Li, Y.; Syed, J.; Sugiyama, H. RNA-DNA Triplex Formation by Long Noncoding RNAs. Cell Chem. Biol. 2016, 23, 1325–1333.
  35. Diederichs, S. The Four Dimensions of Noncoding RNA Conservation. Trends Genet. 2014, 30, 121–123.
  36. Pan, J.; Wang, R.; Shang, F.; Ma, R.; Rong, Y.; Zhang, Y. Functional Micropeptides Encoded by Long Non-Coding RNAs: A Comprehensive Review. Front. Mol. Biosci. 2022, 9, 817517.
  37. Salmena, L.; Poliseno, L.; Tay, Y.; Kats, L.; Pandolfi, P.P. A CeRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? Cell 2011, 146, 353–358.
  38. Tay, Y.; Rinn, J.; Pandolfi, P.P. The Multilayered Complexity of CeRNA Crosstalk and Competition. Nature 2014, 505, 344–352.
  39. Chan, J.J.; Tay, Y. Noncoding RNA:RNA Regulatory Networks in Cancer. Int. J. Mol. Sci. 2018, 19, 1310.
  40. Siniscalchi, C.; Di Palo, A.; Russo, A.; Potenza, N. The LncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation. Int. J. Mol. Sci. 2022, 23, 611.
  41. Wong, L.-S.; Wong, C.-M. Decoding the Roles of Long Noncoding RNAs in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2021, 22, 3137.
  42. Ogawa, Y.; Sun, B.K.; Lee, J.T. Intersection of the RNA Interference and X-Inactivation Pathways. Science 2008, 320, 1336–1341.
  43. Nolasco, S.; Bellido, J.; Gonçalves, J.; Tavares, A.; Zabala, J.C.; Soares, H. The Expression of Tubulin Cofactor A (TBCA) Is Regulated by a Noncoding Antisense Tbca RNA during Testis Maturation. PLoS ONE 2012, 7, e42536.
  44. Lipovich, L.; Dachet, F.; Cai, J.; Bagla, S.; Balan, K.; Jia, H.; Loeb, J.A. Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks. Genetics 2012, 192, 1133–1148.
  45. Bo, C.; Li, X.; He, L.; Zhang, S.; Li, N.; An, Y. A Novel Long Noncoding RNA HHIP-AS1 Suppresses Hepatocellular Carcinoma Progression through Stabilizing HHIP MRNA. Biochem. Biophys. Res. Commun. 2019, 520, 333–340.
  46. Volders, P.-J.; Anckaert, J.; Verheggen, K.; Nuytens, J.; Martens, L.; Mestdagh, P.; Vandesompele, J. LNCipedia 5: Towards a Reference Set of Human Long Non-Coding RNAs. Nucleic Acids Res. 2019, 47, D135–D139.
  47. Cai, H.; Zheng, Y.; Wen, Z.; Yang, Y.; Yang, S.; Zhang, Q. LncRNA AIRN Influences the Proliferation and Apoptosis of Hepatocellular Carcinoma Cells by Regulating STAT1 Ubiquitination. Arch. Pharmacol. Res. 2021, 44, 414–426.
  48. Lu, Q.; Wang, H.; Lei, X.; Ma, Q.; Zhao, J.; Sun, W.; Guo, C.; Huang, D.; Xu, Q. LncRNA ALKBH3-AS1 Enhances ALKBH3 MRNA Stability to Promote Hepatocellular Carcinoma Cell Proliferation and Invasion. J. Cell Mol. Med. 2022, 26, 5292–5302.
  49. Huang, M.; Chen, W.; Qi, F.; Xia, R.; Sun, M.; Xu, T.; Yin, L.; Zhang, E.; De, W.; Shu, Y. Long Non-Coding RNA ANRIL Is Upregulated in Hepatocellular Carcinoma and Regulates Cell Apoptosis by Epigenetic Silencing of KLF2. J. Hematol. Oncol. 2015, 8, 50.
  50. Huang, Y.; Xiang, B.; Liu, Y.; Wang, Y.; Kan, H. LncRNA CDKN2B-AS1 Promotes Tumor Growth and Metastasis of Human Hepatocellular Carcinoma by Targeting Let-7c-5p/NAP1L1 Axis. Cancer Lett. 2018, 437, 56–66.
  51. Huang, D.; Bi, C.; Zhao, Q.; Ding, X.; Bian, C.; Wang, H.; Wang, T.; Liu, H. Knockdown Long Non-Coding RNA ANRIL Inhibits Proliferation, Migration and Invasion of HepG2 Cells by down-Regulation of MiR-191. BMC Cancer 2018, 18, 919.
  52. Chen, J.; Huang, X.; Wang, W.; Xie, H.; Li, J.; Hu, Z.; Zheng, Z.; Li, H.; Teng, L. LncRNA CDKN2BAS Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma and Promotes Metastasis via the MiR-153-5p/ARHGAP18 Signaling Axis. Aging 2018, 10, 3371–3381.
  53. Li, K.; Zhao, B.; Wei, D.; Cui, Y.; Qian, L.; Wang, W.; Liu, G. Long Non-Coding RNA ANRIL Enhances Mitochondrial Function of Hepatocellular Carcinoma by Regulating the MiR-199a-5p/ARL2 Axis. Environ. Toxicol. 2020, 35, 313–321.
  54. Ma, J.; Li, T.; Han, X.; Yuan, H. Knockdown of LncRNA ANRIL Suppresses Cell Proliferation, Metastasis, and Invasion via Regulating MiR-122-5p Expression in Hepatocellular Carcinoma. J. Cancer Res. Clin. Oncol. 2018, 144, 205–214.
  55. Tian, Q.; Yan, X.; Yang, L.; Liu, Z.; Yuan, Z.; Zhang, Y. Long Non-Coding RNA BACE1-AS Plays an Oncogenic Role in Hepatocellular Carcinoma Cells through MiR-214-3p/APLN Axis. Acta Biochim. Biophys. Sin. 2021, 53, 1538–1546.
  56. Yang, Y.; Ge, H.; Li, D.; Xu, A. E2F1-Induced LncRNA BAIAP2-AS1 Overexpression Contributes to the Malignant Progression of Hepatocellular Carcinoma via MiR-361-3p/SOX4 Axis. Dis. Markers 2021, 2021, e6256369.
  57. Ma, Y.; Sun, W.; Zhang, Q.; Gao, B.; Cai, W.; Liu, Q.; Liao, J.; Wang, X. LncRNA BSG-AS1 Is Hypoxia-Responsive and Promotes Hepatocellular Carcinoma by Enhancing BSG MRNA Stability. Biochem. Biophys. Res. Commun. 2021, 566, 101–107.
  58. Feng, Y.; Wei, G.; Zhang, L.; Zhou, H.; Wang, W.; Guo, P.; Cheng, C.; Ji, L.; Cai, Q.; Feng, Y.; et al. LncRNA DARS-AS1 Aggravates the Growth and Metastasis of Hepatocellular Carcinoma via Regulating the MiR-3200-5p-Cytoskeleton Associated Protein 2 (CKAP2) Axis. Bioengineered 2021, 12, 8217–8232.
  59. Wan, T.; Zheng, J.; Yao, R.; Yang, S.; Zheng, W.; Zhou, P. LncRNA DDX11-AS1 Accelerates Hepatocellular Carcinoma Progression via the MiR-195-5p/MACC1 Pathway. Ann. Hepatol. 2021, 20, 100258.
  60. Min, J.; Jin, D.; Zhang, F.; Kang, Y.; Qi, Y.; Du, P. DLG1-AS1 Is Activated by MYC and Drives the Proliferation and Migration of Hepatocellular Carcinoma Cells through MiR-497-5p/SSRP1 Axis. Cancer Cell Int. 2021, 21, 16.
  61. Peng, X.; Wei, F.; Hu, X. Long Noncoding RNA DLGAP1-AS1 Promotes Cell Proliferation in Hepatocellular Carcinoma via Sequestering MiR-486-5p. J. Cell Biochem. 2020, 121, 1953–1962.
  62. Fu, C.; Li, J.; Li, P.; Cheng, D. LncRNA DNAJC3-AS1 Promotes Hepatocellular Carcinoma (HCC) Progression via Sponging Premature MiR-27b. Cancer Manag. Res. 2021, 13, 8575–8583.
  63. Liu, X.; Peng, D.; Cao, Y.; Zhu, Y.; Yin, J.; Zhang, G.; Peng, X.; Meng, Y. Upregulated LncRNA DLX6-AS1 Underpins Hepatocellular Carcinoma Progression via the MiR-513c/Cul4A/ANXA10 Axis. Cancer Gene Ther. 2021, 28, 486–501.
  64. Li, D.; Tang, X.; Li, M.; Zheng, Y. Long Noncoding RNA DLX6-AS1 Promotes Liver Cancer by Increasing the Expression of WEE1 via Targeting MiR-424-5p. J. Cell Biochem. 2019, 120, 12290–12299.
  65. Ma, Y.-K.; Shen, T.-H.; Yang, X.-Y. Upregulation of LncRNA FAM83H-AS1 in Hepatocellular Carcinoma Promotes Cell Proliferation, Migration and Invasion by Wnt/β-Catenin Pathway. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 7855–7862.
  66. Zhuang, J.; He, S.; Wang, G.; Wang, G.; Ni, J.; Zhang, S.; Ye, Y.; Xia, W. Long Noncoding RNA FGFR3-AS1 Promotes Hepatocellular Carcinoma Carcinogenesis via Modulating the PI3K/AKT Pathway. Oncol. Res. 2018, 26, 1257–1265.
  67. Luo, X.; Zhou, N.; Wang, L.; Zeng, Q.; Tang, H. Long Noncoding RNA GATA3-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Suppression of PTEN, CDKN1A, and TP53. Can. J. Gastroenterol. Hepatol. 2019, 2019, 1389653.
  68. Zhu, X.-T.; Yuan, J.-H.; Zhu, T.-T.; Li, Y.-Y.; Cheng, X.-Y. Long Noncoding RNA Glypican 3 (GPC3) Antisense Transcript 1 Promotes Hepatocellular Carcinoma Progression via Epigenetically Activating GPC3. FEBS J. 2016, 283, 3739–3754.
  69. Yang, L.; Zhang, X.; Li, H.; Liu, J. The Long Noncoding RNA HOTAIR Activates Autophagy by Upregulating ATG3 and ATG7 in Hepatocellular Carcinoma. Mol. Biosyst. 2016, 12, 2605–2612.
  70. Ding, C.; Cheng, S.; Yang, Z.; Lv, Z.; Xiao, H.; Du, C.; Peng, C.; Xie, H.; Zhou, L.; Wu, J.; et al. Long Non-Coding RNA HOTAIR Promotes Cell Migration and Invasion via down-Regulation of RNA Binding Motif Protein 38 in Hepatocellular Carcinoma Cells. Int. J. Mol. Sci. 2014, 15, 4060–4076.
  71. Gao, J.-Z.; Li, J.; Du, J.-L.; Li, X.-L. Long Non-Coding RNA HOTAIR Is a Marker for Hepatocellular Carcinoma Progression and Tumor Recurrence. Oncol. Lett. 2016, 11, 1791–1798.
  72. Zhou, J.-J.; Cheng, D.; He, X.-Y.; Meng, Z.; Li, W.-Z.; Chen, R.-F. Knockdown of Hotair Suppresses Proliferation and Cell Cycle Progression in Hepatocellular Carcinoma Cell by Downregulating CCND1 Expression. Mol. Med. Rep. 2017, 16, 4980–4986.
  73. Wei, S.; Fan, Q.; Yang, L.; Zhang, X.; Ma, Y.; Zong, Z.; Hua, X.; Su, D.; Sun, H.; Li, H.; et al. Promotion of Glycolysis by HOTAIR through GLUT1 Upregulation via MTOR Signaling. Oncol. Rep. 2017, 38, 1902–1908.
  74. Hu, M.; Fu, Q.; Jing, C.; Zhang, X.; Qin, T.; Pan, Y. LncRNA HOTAIR Knockdown Inhibits Glycolysis by Regulating MiR-130a-3p/HIF1A in Hepatocellular Carcinoma under Hypoxia. Biomed. Pharmacol. 2020, 125, 109703.
  75. Su, D.-N.; Wu, S.-P.; Chen, H.-T.; He, J.-H. HOTAIR, a Long Non-Coding RNA Driver of Malignancy Whose Expression Is Activated by FOXC1, Negatively Regulates MiRNA-1 in Hepatocellular Carcinoma. Oncol. Lett. 2016, 12, 4061–4067.
  76. Liu, C.; Shang, Z.; Ma, Y.; Ma, J.; Song, J. HOTAIR/MiR-214-3p/FLOT1 Axis Plays an Essential Role in the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma. Int. J. Clin. Exp. Pathol. 2019, 12, 50–63.
  77. Zhang, Y.; Xu, J.; Zhang, S.; An, J.; Zhang, J.; Huang, J.; Jin, Y. HOXA-AS2 Promotes Proliferation and Induces Epithelial-Mesenchymal Transition via the MiR-520c-3p/GPC3 Axis in Hepatocellular Carcinoma. Cell Physiol. Biochem. 2018, 50, 2124–2138.
  78. Ji, W.; Wang, Q.; Yang, J. LncRNA HOXD-AS1 Promotes the Metastasis of Human Hepatocellular Carcinoma via Modulating MiR-326/SLC27A4. Cancer Cell Int. 2020, 20, 161.
  79. Sun, J.; Guo, Y.; Bie, B.; Zhu, M.; Tian, H.; Tian, J.; Li, J.; Yang, Y.; Ji, F.; Kong, G.; et al. Silencing of Long Noncoding RNA HOXD-AS1 Inhibits Proliferation, Cell Cycle Progression, Migration and Invasion of Hepatocellular Carcinoma Cells through MEK/ERK Pathway. J. Cell Biochem. 2020, 121, 443–457.
  80. Li, C.; Miao, R.; Zhang, J.; Qu, K.; Liu, C. Long Non-Coding RNA KCNQ1OT1 Mediates the Growth of Hepatocellular Carcinoma by Functioning as a Competing Endogenous RNA of MiR-504. Int. J. Oncol. 2018, 52, 1603–1612.
  81. Zhang, L.; Wang, L.; Wang, Y.; Chen, T.; Liu, R.; Yang, W.; Liu, Q.; Tu, K. LncRNA KTN1-AS1 Promotes Tumor Growth of Hepatocellular Carcinoma by Targeting MiR-23c/ERBB2IP Axis. Biomed. Pharmacol. 2019, 109, 1140–1147.
  82. Yin, L.; Chen, Y.; Zhou, Y.; Deng, G.; Han, Y.; Guo, C.; Li, Y.; Zeng, S.; Shen, H. Increased Long Noncoding RNA LASP1-AS Is Critical for Hepatocellular Carcinoma Tumorigenesis via Upregulating LASP1. J. Cell. Physiol. 2019, 234, 13493–13509.
  83. Dong, H.; Jian, P.; Yu, M.; Wang, L. Silencing of Long Noncoding RNA LEF1-AS1 Prevents the Progression of Hepatocellular Carcinoma via the Crosstalk with MicroRNA-136-5p/WNK1. J. Cell. Physiol. 2020, 235, 6548–6562.
  84. Feng, Z.; Ye, Z.; Xie, J.; Chen, W.; Li, W.; Xing, C. Study on the Mechanism of LOXL1-AS1/MiR-3614-5p/YY1 Signal Axis in the Malignant Phenotype Regulation of Hepatocellular Carcinoma. Biol. Direct 2021, 16, 24.
  85. Guo, Y.; Zhong, J.; Wu, F.; Zhan, Z. Long Noncoding RNA MACC1-AS1 Promotes the Stemness of Hepatocellular Carcinoma Cells by Antagonizing MiR-145. J. Int. Med. Res. 2020, 48, 300060520920411.
  86. Tong, H.; Liu, X.; Li, T.; Qiu, W.; Peng, C.; Shen, B.; Zhu, Z. MACC1-AS1 Promotes Hepatocellular Carcinoma Cell Invasion and Proliferation by Regulating PAX8. Aging 2020, 12, 70–79.
  87. Ouyang, H.; Zhang, L.; Xie, Z.; Ma, S. Long Noncoding RNA MAFG-AS1 Promotes Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cells through Downregulation of MiR-6852. Exp. Med. 2019, 18, 2547–2553.
  88. Wang, L.; Sun, L.; Liu, R.; Mo, H.; Niu, Y.; Chen, T.; Wang, Y.; Han, S.; Tu, K.; Liu, Q. Long Non-Coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α Signaling Loop Promotes Hepatocellular Carcinoma Progression. J. Exp. Clin. Cancer Res. 2021, 40, 72.
  89. Wang, Y.; Yang, L.; Chen, T.; Liu, X.; Guo, Y.; Zhu, Q.; Tong, X.; Yang, W.; Xu, Q.; Huang, D.; et al. A Novel LncRNA MCM3AP-AS1 Promotes the Growth of Hepatocellular Carcinoma by Targeting MiR-194-5p/FOXA1 Axis. Mol. Cancer 2019, 18, 28.
  90. Wei, Y.; Wang, Z.; Zong, Y.; Deng, D.; Chen, P.; Lu, J. LncRNA MFI2-AS1 Promotes HCC Progression and Metastasis by Acting as a Competing Endogenous RNA of MiR-134 to Upregulate FOXM1 Expression. Biomed. Pharmacol. 2020, 125, 109890.
  91. Pan, G.; Zhang, J.; You, F.; Cui, T.; Luo, P.; Wang, S.; Li, X.; Yuan, Q. ETS Proto-Oncogene 1-Activated Muskelin 1 Antisense RNA Drives the Malignant Progression of Hepatocellular Carcinoma by Targeting MiR-22-3p to Upregulate ETS Proto-Oncogene 1. Bioengineered 2022, 13, 1346–1358.
  92. Gao, W.; Chen, X.; Chi, W.; Xue, M. Long Non-coding RNA MKLN1-AS Aggravates Hepatocellular Carcinoma Progression by Functioning as a Molecular Sponge for MiR-654-3p, Thereby Promoting Hepatoma-derived Growth Factor Expression. Int. J. Mol. Med. 2020, 46, 1743–1754.
  93. Teng, F.; Zhang, J.-X.; Chang, Q.-M.; Wu, X.-B.; Tang, W.-G.; Wang, J.-F.; Feng, J.-F.; Zhang, Z.-P.; Hu, Z.-Q. LncRNA MYLK-AS1 Facilitates Tumor Progression and Angiogenesis by Targeting MiR-424-5p/E2F7 Axis and Activating VEGFR-2 Signaling Pathway in Hepatocellular Carcinoma. J. Exp. Clin. Cancer Res. 2020, 39, 235.
  94. Liu, J.; Zhao, S.-Y.; Jiang, Q.; Qu, Y.; Huang, X.; Du, J.; Sun, W.; Ye, Q. Long Noncoding RNA MYLK-AS1 Promotes Growth and Invasion of Hepatocellular Carcinoma through the EGFR/HER2-ERK1/2 Signaling Pathway. Int. J. Biol. Sci. 2020, 16, 1989–2000.
  95. Wang, Y.; Yang, L.; Dong, X.; Yang, X.; Zhang, X.; Liu, Z.; Zhao, X.; Wen, T. Overexpression of NNT-AS1 Activates TGF-β Signaling to Decrease Tumor CD4 Lymphocyte Infiltration in Hepatocellular Carcinoma. Biomed. Res. Int. 2020, 2020, 8216541.
  96. Lu, Y.-B.; Jiang, Q.; Yang, M.-Y.; Zhou, J.-X.; Zhang, Q. Long Noncoding RNA NNT-AS1 Promotes Hepatocellular Carcinoma Progression and Metastasis through MiR-363/CDK6 Axis. Oncotarget 2017, 8, 88804–88814.
  97. He, H.; Chen, T.; Mo, H.; Chen, S.; Liu, Q.; Guo, C. Hypoxia-Inducible Long Noncoding RNA NPSR1-AS1 Promotes the Proliferation and Glycolysis of Hepatocellular Carcinoma Cells by Regulating the MAPK/ERK Pathway. Biochem. Biophys. Res. Commun. 2020, 533, 886–892.
  98. Li, X.; Li, Y.; Bai, S.; Zhang, J.; Liu, Z.; Yang, J. NR2F1-AS1/MiR-140/HK2 Axis Regulates Hypoxia-Induced Glycolysis and Migration in Hepatocellular Carcinoma. Cancer Manag. Res. 2021, 13, 427–437.
  99. Kong, S.; Xue, H.; Li, Y.; Li, P.; Ma, F.; Liu, M.; Li, W. The Long Noncoding RNA OTUD6B-AS1 Enhances Cell Proliferation and the Invasion of Hepatocellular Carcinoma Cells through Modulating GSKIP/Wnt/β-Catenin Signalling via the Sequestration of MiR-664b-3p. Exp. Cell Res. 2020, 395, 112180.
  100. Yuan, S.-X.; Tao, Q.-F.; Wang, J.; Yang, F.; Liu, L.; Wang, L.-L.; Zhang, J.; Yang, Y.; Liu, H.; Wang, F.; et al. Antisense Long Non-Coding RNA PCNA-AS1 Promotes Tumor Growth by Regulating Proliferating Cell Nuclear Antigen in Hepatocellular Carcinoma. Cancer Lett. 2014, 349, 87–94.
  101. Sun, J.; Zhang, Y.; Li, B.; Dong, Y.; Sun, C.; Zhang, F.; Jin, L.; Chen, D.; Wang, W. PITPNA-AS1 Abrogates the Inhibition of MiR-876-5p on WNT5A to Facilitate Hepatocellular Carcinoma Progression. Cell Death Dis. 2019, 10, 844.
  102. Ou, Y.; Deng, Y.; Wang, H.; Zhang, Q.; Luo, H.; Hu, P. Targeting Antisense LncRNA PRKAG2-AS1, as a Therapeutic Target, Suppresses Malignant Behaviors of Hepatocellular Carcinoma Cells. Front. Med. 2021, 8, 649279.
  103. Qin, M.; Meng, Y.; Luo, C.; He, S.; Qin, F.; Yin, Y.; Huang, J.; Zhao, H.; Hu, J.; Deng, Z.; et al. LncRNA PRR34-AS1 Promotes HCC Development via Modulating Wnt/β-Catenin Pathway by Absorbing MiR-296-5p and Upregulating E2F2 and SOX12. Mol. Ther.-Nucleic Acids 2021, 25, 37–52.
  104. Zhang, Z.; Zhou, Y.; Jia, Y.; Wang, C.; Zhang, M.; Xu, Z. PRR34-AS1 Promotes Exosome Secretion of VEGF and TGF-β via Recruiting DDX3X to Stabilize Rab27a MRNA in Hepatocellular Carcinoma. J. Transl. Med. 2022, 20, 491.
  105. Yang, X.; Song, D.; Zhang, J.; Yang, X.; Feng, H.; Guo, J. PRR34-AS1 Sponges MiR-498 to Facilitate TOMM20 and ITGA6 Mediated Tumor Progression in HCC. Exp. Mol. Pathol. 2021, 120, 104620.
  106. Mu, J.-Y.; Tian, X.-J.; Chen, Y.-J. LncRNA RBM5-AS1 Promotes Cell Proliferation and Invasion by Epigenetically Silencing MiR-132/212 in Hepatocellular Carcinoma Cells. Cell Biol. Int. 2021, 45, 2201–2210.
  107. Zhang, X.; Yan, Z.; Wang, L.; Zhang, S.; Gao, M. STAT1-Induced Upregulation of LncRNA RHPN1-AS1 Predicts a Poor Prognosis of Hepatocellular Carcinoma and Contributes to Tumor Progression via the MiR-485/CDCA5 Axis. J. Cell Biochem. 2020, 121, 4741–4755.
  108. Fen, H.; Hongmin, Z.; Wei, W.; Chao, Y.; Yang, Y.; Bei, L.; Zhihua, S. RHPN1-AS1 Drives the Progression of Hepatocellular Carcinoma via Regulating MiR-596/IGF2BP2 Axis. Curr. Pharmacol. Des. 2020, 25, 4630–4640.
  109. Huang, C.; Li, K.; Huang, R.; Zhu, J.; Yang, J. RNF185-AS1 Promotes Hepatocellular Carcinoma Progression through Targeting MiR-221-5p/Integrin Β5 Axis. Life Sci. 2021, 267, 118928.
  110. Li, Y.; Liu, G.; Li, X.; Dong, H.; Xiao, W.; Lu, S. Long Non-Coding RNA SBF2-AS1 Promotes Hepatocellular Carcinoma Progression through Regulation of MiR-140-5p-TGFBR1 Pathway. Biochem. Biophys. Res. Commun. 2018, 503, 2826–2832.
  111. Li, Y.; Guo, D.; Lu, G.; Mohiuddin Chowdhury, A.T.M.; Zhang, D.; Ren, M.; Chen, Y.; Wang, R.; He, S. LncRNA SNAI3-AS1 Promotes PEG10-Mediated Proliferation and Metastasis via Decoying of MiR-27a-3p and MiR-34a-5p in Hepatocellular Carcinoma. Cell Death Dis. 2020, 11, 685.
  112. Zhang, W.; Wu, Y.; Hou, B.; Wang, Y.; Deng, D.; Fu, Z.; Xu, Z. A SOX9-AS1/MiR-5590-3p/SOX9 Positive Feedback Loop Drives Tumor Growth and Metastasis in Hepatocellular Carcinoma through the Wnt/β-Catenin Pathway. Mol. Oncol. 2019, 13, 2194–2210.
  113. Di Palo, A.; Siniscalchi, C.; Mosca, N.; Russo, A.; Potenza, N. A Novel CeRNA Regulatory Network Involving the Long Non-Coding Antisense RNA SPACA6P-AS, MiR-125a and Its MRNA Targets in Hepatocarcinoma Cells. Int. J. Mol. Sci. 2020, 21, 5068.
  114. Kuai, J.; Zheng, L.; Yi, X.; Liu, Z.; Qiu, B.; Lu, Z.; Jiang, Y. ST8SIA6-AS1 Promotes the Development of Hepatocellular Carcinoma Cells through MiR-338-3p/NONO Axis. Dig. Liver Dis. 2021, 53, 1192–1200.
  115. Li, Y.; Jiang, A. ST8SIA6-AS1 Promotes Hepatocellular Carcinoma by Absorbing MiR-5195-3p to Regulate HOXB6. Cancer Biol. Ther. 2020, 21, 647–655.
  116. Huang, W.; Chen, Q.; Dai, J.; Zhang, Y.; Yi, Y.; Wei, X. Long Noncoding TMPO Antisense RNA 1 Promotes Hepatocellular Carcinoma Proliferation and Epithelial-Mesenchymal Transition by Targeting the MicroRNA-126-3p/LRP6/β-Catenin Axis. Ann. Transl. Med. 2021, 9, 1679.
  117. Guo, X.; Wang, Y. LncRNA TMPO-AS1 Promotes Hepatocellular Carcinoma Cell Proliferation, Migration and Invasion through Sponging MiR-329-3p to Stimulate FOXK1-Mediated AKT/MTOR Signaling Pathway. Cancer Med. 2020, 9, 5235–5246.
  118. Wang, Z.; Huang, D.; Huang, J.; Nie, K.; Li, X.; Yang, X. LncRNA TMPO-AS1 Exerts Oncogenic Roles in HCC Through Regulating MiR-320a/SERBP1 Axis. OncoTargets Ther. 2020, 13, 6539–6551.
  119. Li, S.; Huang, Y.; Huang, Y.; Fu, Y.; Tang, D.; Kang, R.; Zhou, R.; Fan, X.-G. The Long Non-Coding RNA TP73-AS1 Modulates HCC Cell Proliferation through MiR-200a-Dependent HMGB1/RAGE Regulation. J. Exp. Clin. Cancer Res. 2017, 36, 51.
  120. Sun, X.; Qian, Y.; Wang, X.; Cao, R.; Zhang, J.; Chen, W.; Fang, M. LncRNA TRG-AS1 Stimulates Hepatocellular Carcinoma Progression by Sponging MiR-4500 to Modulate BACH1. Cancer Cell Int. 2020, 20, 367.
  121. Zhou, C.; Chen, Z.; Peng, C.; Chen, C.; Li, H. Long Noncoding RNA TRIM52-AS1 Sponges MiR-514a-5p to Facilitate Hepatocellular Carcinoma Progression Through Increasing MRPS18A. Cancer Biother. Radiopharm. 2021, 36, 211–219.
  122. Zhu, X.; Jiang, S.; Wu, Z.; Liu, T.; Zhang, W.; Wu, L.; Xu, L.; Shao, M. Long Non-Coding RNA TTN Antisense RNA 1 Facilitates Hepatocellular Carcinoma Progression via Regulating MiR-139-5p/SPOCK1 Axis. Bioengineered 2021, 12, 578–588.
  123. Huang, X.; Pan, J.; Wang, G.; Huang, T.; Li, C.; Wang, Y.; Li, X. UNC5B-AS1 Promotes the Proliferation, Migration and EMT of Hepatocellular Carcinoma Cells via Regulating MiR-4306/KDM2A Axis. Cell Cycle 2021, 20, 2114–2124.
  124. Zhang, D.-Y.; Sun, Q.-C.; Zou, X.-J.; Song, Y.; Li, W.-W.; Guo, Z.-Q.; Liu, S.-S.; Liu, L.; Wu, D.-H. Long Noncoding RNA UPK1A-AS1 Indicates Poor Prognosis of Hepatocellular Carcinoma and Promotes Cell Proliferation through Interaction with EZH2. J. Exp. Clin. Cancer Res. 2020, 39, 229.
  125. Chen, S.-P.; Zhu, G.-Q.; Xing, X.-X.; Wan, J.-L.; Cai, J.-L.; Du, J.-X.; Song, L.-N.; Dai, Z.; Zhou, J. LncRNA USP2-AS1 Promotes Hepatocellular Carcinoma Growth by Enhancing YBX1-Mediated HIF1α Protein Translation Under Hypoxia. Front. Oncol. 2022, 12, 882372.
  126. Fa, X.; Song, P.; Fu, Y.; Deng, Y.; Liu, K. Long Non-Coding RNA VPS9D1-AS1 Facilitates Cell Proliferation, Migration and Stemness in Hepatocellular Carcinoma. Cancer Cell Int. 2021, 21, 131.
  127. Hu, Z.; Huang, P.; Yan, Y.; Zhou, Z.; Wang, J.; Wu, G. Hepatitis B Virus X Protein Related LncRNA WEE2-AS1 Promotes Hepatocellular Carcinoma Proliferation and Invasion. Biochem. Biophys. Res. Commun. 2019, 508, 79–86.
  128. Mu, B.; Lv, C.; Liu, Q.; Yang, H. Long Non-Coding RNA ZEB1-AS1 Promotes Proliferation and Metastasis of Hepatocellular Carcinoma Cells by Targeting MiR-299-3p/E2F1 Axis. J. Biochem. 2021, 170, 41–50.
  129. Xue, S.; Lu, F.; Sun, C.; Zhao, J.; Zhen, H.; Li, X. LncRNA ZEB1-AS1 Regulates Hepatocellular Carcinoma Progression by Targeting MiR-23c. World J. Surg. Oncol. 2021, 19, 121.
  130. Ma, Z.-J.; Wang, Y.; Li, H.-F.; Liu, M.-H.; Bi, F.-R.; Ma, L.; Ma, H.; Yan, H.-L. LncZEB1-AS1 Regulates Hepatocellular Carcinoma Bone Metastasis via Regulation of the MiR-302b-EGFR-PI3K-AKT Axis. J. Cancer 2020, 11, 5118–5128.
  131. Wu, S.M.; Chen, J.; Liang, Y.; Luo, Q.; Tong, Y.Y.; Xie, L. Long Non-Coding RNA ZEB2-AS1 Promotes Hepatocellular Carcinoma Progression by Regulating The MiR-582-5p/FOXC1 Axis. Cell J. 2022, 24, 285–293.
  132. Duan, R.; Li, C.; Wang, F.; Han, F.; Zhu, L. The Long Noncoding RNA ZFAS1 Potentiates the Development of Hepatocellular Carcinoma via the MicroRNA-624/MDK/ERK/JNK/P38 Signaling Pathway. Onco Targets 2020, 13, 4431–4444.
  133. Liu, W.; Zhang, G.-Q.; Zhu, D.-Y.; Wang, L.-J.; Li, G.-T.; Xu, J.-G.; Jin, X.-L.; Zhu, Y.-M.; Yang, X.-Y. Long Noncoding RNA ZFPM2-AS1 Regulates ITGB1 by MiR-1226-3p to Promote Cell Proliferation and Invasion in Hepatocellular Carcinoma. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 7612–7620.
  134. Liu, J.; Zhang, H.; Xia, P.; Zhu, Y.; Xu, K.; Liu, Z.; Yuan, Y. Genome Stability-related LncRNA ZFPM2-AS1 Promotes Tumor Progression via MiR-3065-5p/XRCC4 in Hepatocellular Carcinoma. Int. J. Oncol. 2023, 62, 19.
  135. He, H.; Wang, Y.; Ye, P.; Yi, D.; Cheng, Y.; Tang, H.; Zhu, Z.; Wang, X.; Jin, S. Long Noncoding RNA ZFPM2-AS1 Acts as a MiRNA Sponge and Promotes Cell Invasion through Regulation of MiR-139/GDF10 in Hepatocellular Carcinoma. J. Exp. Clin. Cancer Res. 2020, 39, 159.
  136. Zhang, X.-W.; Li, Q.-H.; Xu, Z.; Dou, J.-J. STAT1-Induced Regulation of LncRNA ZFPM2-AS1 Predicts Poor Prognosis and Contributes to Hepatocellular Carcinoma Progression via the MiR-653/GOLM1 Axis. Cell Death Dis. 2021, 12, 31.
  137. Lv, C.; Wan, Q.; Shen, C.; Wu, H.; Zhou, B.; Wang, W. Long Non-coding RNA ZSCAN16-AS1 Promotes the Malignant Properties of Hepatocellular Carcinoma by Decoying MicroRNA-451a and Consequently Increasing ATF2 Expression. Mol. Med. Rep. 2021, 24, 780.
  138. Liu, J.; Liu, R.; Liu, Y.; Li, L.; Cao, H.; Liu, J.; Cao, G. ZSCAN16-AS1 Expedites Hepatocellular Carcinoma Progression via Modulating the MiR-181c-5p/SPAG9 Axis to Activate the JNK Pathway. Cell Cycle 2021, 20, 1134–1146.
  139. Pu, J.; Zhang, Y.; Wang, A.; Qin, Z.; Zhuo, C.; Li, W.; Xu, Z.; Tang, Q.; Wang, J.; Wei, H. ADORA2A-AS1 Restricts Hepatocellular Carcinoma Progression via Binding HuR and Repressing FSCN1/AKT Axis. Front. Oncol. 2021, 11, 4081.
  140. Wang, F.; Qi, X.; Li, Z.; Jin, S.; Xie, Y.; Zhong, H. LncRNA CADM1-AS1 Inhibits Cell-Cycle Progression and Invasion via PTEN/AKT/GSK-3β Axis in Hepatocellular Carcinoma. Cancer Manag. Res. 2019, 11, 3813–3828.
  141. Deng, Y.; Wei, Z.; Huang, M.; Xu, G.; Wei, W.; Peng, B.; Nong, S.; Qin, H. Long Non-Coding RNA F11-AS1 Inhibits HBV-Related Hepatocellular Carcinoma Progression by Regulating NR1I3 via Binding to MicroRNA-211-5p. J. Cell Mol. Med. 2020, 24, 1848–1865.
  142. Ding, C.-H.; Yin, C.; Chen, S.-J.; Wen, L.-Z.; Ding, K.; Lei, S.-J.; Liu, J.-P.; Wang, J.; Chen, K.-X.; Jiang, H.-L.; et al. The HNF1α-Regulated LncRNA HNF1A-AS1 Reverses the Malignancy of Hepatocellular Carcinoma by Enhancing the Phosphatase Activity of SHP-1. Mol. Cancer 2018, 17, 63.
  143. Wei, H.; Tang, Q.; Wang, A.; Zhang, Y.; Qin, Z.; Li, W.; Xu, Z.; Wang, J.; Pu, J. LncRNA MAGI2-AS3 Exerts Antioncogenic Roles in Hepatocellular Carcinoma via Regulating the MiR-519c-3p/TXNIP Axis. J. Oncol. 2021, 2021, 5547345.
  144. Pu, J.; Wang, J.; Wei, H.; Lu, T.; Wu, X.; Wu, Y.; Shao, Z.; Luo, C.; Lu, Y. LncRNA MAGI2-AS3 Prevents the Development of HCC via Recruiting KDM1A and Promoting H3K4me2 Demethylation of the RACGAP1 Promoter. Mol. Ther.-Nucleic Acids 2019, 18, 351–362.
  145. Liu, Y.; Liu, R.; Zhao, J.; Zeng, Z.; Shi, Z.; Lu, Q.; Guo, J.; Li, L.; Yao, Y.; Liu, X.; et al. LncRNA TMEM220-AS1 Suppresses Hepatocellular Carcinoma Cell Proliferation and Invasion by Regulating the TMEM220/β-Catenin Axis. J. Cancer 2021, 12, 6805–6813.
  146. Zhang, R.; Wei, Y.; Zhu, L.; Huang, L.; Wei, Y.; Chen, G.; Dang, Y.; Feng, Z. LncRNA UCHL1-AS1 Prevents Cell Mobility of Hepatocellular Carcinoma: A Study Based on in Vitro and Bioinformatics. Int. J. Clin. Exp. Pathol. 2018, 11, 2270–2280.
  147. Lv, L.; Chen, G.; Zhou, J.; Li, J.; Gong, J. WT1-AS Promotes Cell Apoptosis in Hepatocellular Carcinoma through down-Regulating of WT1. J. Exp. Clin. Cancer Res. 2015, 34, 119.
  148. Xu, D.; Liu, X.; Wu, J.; Wang, Y.; Zhou, K.; Chen, W.; Chen, J.; Chen, C.; Chen, L. LncRNA WWOX-AS1 Sponges MiR-20b-5p in Hepatocellular Carcinoma and Represses Its Progression by Upregulating WWOX. Cancer Biol. Ther. 2020, 21, 927–936.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
ScholarVision Creations
Feedback