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.
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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] |
This entry is adapted from the peer-reviewed paper 10.3390/ijms24108886