You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Weidong Yu + 2670 word(s) 2670 2022-03-06 13:45:14 |
2 Format change Jessie Wu Meta information modification 2670 2022-03-23 06:35:37 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Yu, W. Long Non-Coding RNAs in Lung Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/20896 (accessed on 20 December 2025).
Yu W. Long Non-Coding RNAs in Lung Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/20896. Accessed December 20, 2025.
Yu, Weidong. "Long Non-Coding RNAs in Lung Cancer" Encyclopedia, https://encyclopedia.pub/entry/20896 (accessed December 20, 2025).
Yu, W. (2022, March 23). Long Non-Coding RNAs in Lung Cancer. In Encyclopedia. https://encyclopedia.pub/entry/20896
Yu, Weidong. "Long Non-Coding RNAs in Lung Cancer." Encyclopedia. Web. 23 March, 2022.
Long Non-Coding RNAs in Lung Cancer
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cells8091015

Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. 

lncRNAs cancer metastasis

1. LncRNAs Definition and Functions

LncRNAs are a class of RNA transcripts with a length greater than 200 bp, characterized by more spatial and temporal specificity and lower interspecific conservation when compared with mRNAs [1]. LncRNAs had been previously considered to be the by-products of the transcription process. However, it has been widely accepted now that lncRNAs are involved in the process of cell differentiation and growth and the pathogenesis of many diseases, including cancer [2]. According to the relative location of lncRNAs to protein-encoding genes in the genome, they have been classified into sense lncRNA, antisense lncRNA, bidirectional lncRNA, intron lncRNA, intergenic lncRNA, and enhancer lncRNA [3]. So far, lncRNAs have been revealed to play an important role in regulating gene expression at the epigenetic, transcription, and post-transcriptional levels [4].
Firstly, lncRNAs play a crucial role in regulating gene expression though chromatin modification and remodeling, histone modification, and nucleosome localization changes [5]. Among the mechanisms regulating chromosome remodeling, SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a chromosome reconstitution complex composed of multiple subunits, which drive the change of nucleosome localization [6][7]. LncRNAs can interact with SWI/SNF complexes to alter chromosome structure and regulate gene expression [8][9][10][11]. In addition, lncRNAs also regulate chromatin remodeling by affecting the DNA methylation with S-adenosylhomocysteine hydrolase [12], DNA demethylation with growth arrest and DNA-damage-inducible alpha (GADD45A) [13], and acetylation of histone with Sirtuin 6 (SIRT6) [14]. Histone is an important basic unit of the nucleosome, which plays an important role in the formation of structure and function of chromosomes. Many lncRNAs modulate histone methylation by interacting with polycomb repressive complex 2 (PRC2), altering the structure and function of chromosomes [15][16].
Furthermore, microRNAs (miRNAs) inhibit the translation efficiency and/or induce mRNA degradation of the target gene by complementary pairing with the target RNA, regulating gene expression at the post-transcriptional level. There is a type of competitive endogenous RNA (ceRNA) that can indirectly regulate the expression of target genes via competitively binding with miRNAs; this competitive binding of miRNAs is also called microRNA sponges [17][18]. Many lncRNAs can work as miRNA sponges to influence gene expression and the development of cancer [19].

2. LncRNAs in Lung Cancer (LC)

LC is the leading cause of cancer-related deaths, accounting for 18.4% of total cancer-related deaths and taking the first place with an incidence rate of 11.6% among males and females [20]. It was estimated that there were 2,093,876 newly diagnosed LC cases and 1,761,007 cases that died from LC worldwide in 2018 [20][21]. LC is pathologically divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which accounts for 80–85% of all LC cases. NSCLC is further divided into lung squamous cell carcinoma (LSCC), lung adenocarcinoma (LAD), and large cell carcinoma (LCC) [22][23]. Although many advances had been made in the treatment of LC, such as surgical resection and chemotherapy in the past decades, the five-year survival rate is only 15% [22] due to its late-stage diagnosis, metastasis, insensitivity to chemotherapy, and recurrence [22][24]. Clearly, to explore new targets and biomarkers for early diagnosis and more effective treatment of LC is of great significance. In particular, several lncRNAs have been shown to have the potential of serving as novel biomarkers and targets for LC diagnosis and treatment [25].

2.1. Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1)

MALAT1, also known as nuclear-enriched abundant transcript 2 (NEAT2), is an 8.7 kb intergenic lncRNA located on chromosome 11q13 [25], and is one of the most abundantly expressed lncRNAs in normal tissues [26]. MALAT1 is involved in post-transcriptional regulation of gene expression and mRNA splicing [27]. It has been reported that MALAT1 is involved in the pathogenesis of LC and other human cancers, including liver, breast, colon, uterus, prostate, ovarian, and hematological malignancies and neuroblastoma [22][28][29][30].
Several studies have suggested that MALAT1 could serve as a potential prognostic biomarker and therapeutic target for patients with early-stage LC due to its specificity and stability [22][26][31][32][33]. It has been shown that the expression of MALAT1 in NSCLC tissues is higher than that in adjacent tissues, and NSCLC patients with high MALAT1 expression have poor overall survival (OS) [32][34][35]. Moreover, the expression of MALAT1 in NSCLC tissues with bone metastasis is higher than that in NSCLC tissues without bone metastasis [36]. MALAT1 expression level is lower in the peripheral whole blood [37] and cellular fraction of human blood [38] in patients with LC than that in healthy subjects. However, the expression of MALAT1 in the whole blood of LC patients with metastasis is shown to be higher compared with that in patients with non-metastasis [37]. Moreover, MALAT1 level is significantly upregulated in the whole blood of LC patients with metastasis such as bone or brain metastasis than that in LC patients with lymph node or pleura metastasis [37].
Functionally, MALAT1 is considered as an oncogenic lncRNA because of its role in promoting tumor differentiation, proliferation, migration, invasion, EMT, and chemoresistance [25][22]. Silencing of MALAT1 inhibits cell proliferation and colony formation in NSCLC cell lines [31][39][40]. MALAT1 promotes cell migration and invasion process by sponging miR-206 in A549 and H1299 cell lines [41]. In addition, MALAT1 can promote EMT and invasion of A549 and H1299 cells by upregulating the expression of snail family transcriptional repressor 2 (SLUG) through competitively sponging miR-204 [42]. C-X-C motif chemokine ligand 5 (CXCL5) is a downstream gene of MALAT1, and knockdown of CXCL5 in vitro could inhibit MALAT1-induced cell migration and invasion [34]. In nude mice, the total number and area of lung tumor nodules are significantly reduced in the injection of A549 MALAT1 KO cells compared to A549 MALAT1 wild-type (WT) cells [32]. MALAT1 also directly binds with miR-200a to promote cell proliferation and induce gefitinib resistance in A549 cells [43]. An additional study showed that MALAT1 could promote cisplatin (DDP) resistance by sequestering miR-101-3p and upregulating the expression of myeloid cell leukemia 1 (MCL1) in LC cells [44]. Overall, MALAT1 plays an important role in the progression of LC through multiple mechanisms, and it could serve as a potential biomarker and target for the diagnosis and treatment of LC. However, the role of MALAT1 in regulating cancer stemness and post-translational modifications needs to be further studied. In particular, the mechanisms for MALAT1 activation in LC tissues still need further exploration.

2.2. H19

H19 is a 2.3 kb intergenic and maternally-expressed lncRNA located on chromosome 11p15.5, which is also one of the first identified imprinting lncRNA [21][22][28][45]. H19 includes five exons and four introns, and plays an important role in embryonic and tumor development [28][45][46]. H19 is reported to be associated with multiple cancers such as LC, GC, CRC, pancreatic cancer (PC), ovarian cancer (OC), neuroblastoma (NB), and bladder cancer [28][47].
Studies have revealed that the expression of H19 is significantly increased in LC tissues when compared with that in adjacent tissues [21][48]. H19 overexpression is associated with carcinogenesis from early stages to metastasis, reduced disease-free survival (DFS) time, and poor prognosis in LC [25][22][28][49]. Plasma level of H19 is also significantly increased in NSCLC patients, which could be a clinical serological biomarker for complementary diagnosis of NSCLC [50]. In the Chinese population, it has been reported that H19 rs2107425 is significantly related to LC susceptibility [51], and H19 SNP rs217727 is strongly associated with susceptibility to LSCC and LAD [51]. Kaplan–Meier analysis was used to evaluate that higher expressions of H19 and miR-21 are correlated with shorter OS in NSCLC patients, suggesting that H19 and miR-21 together may be involved in the development of LC [52].
H19 plays an important role in promoting cell proliferation and differentiation, cell migration and invasion, and EMT [21]. Zhou et al. reported that knockout of H19 obviously inhibits the proliferation of LC cells in vitro and in vivo [52]. Zhao et al. indicated that the overexpression of H19 sponged and inhibited miR-200a function to upregulate zinc finger E-box binding homeobox 1 (ZEB1) and zinc finger E-box binding homeobox 2 (ZEB2), thereby promoting proliferation, migration, invasion, and EMT in LC [21]. It has been demonstrated that upregulation of H19 can induce cell proliferation, invasion, and EMT occurrence by acting as an miRNA sponge and regulating miRNA-203-mediated EMT [48]. Additionally, H19 can induce cell proliferation by promoting the expression of pro-oncogene lin-28 homolog B (LIN28B) via the inhibition of miR-196b expression in A549 and H1299 LC cell lines [53]. H19 can also compete with miR-107 to bind neurofibromin 1 (NF1), which stimulates the development of NSCLC [23][54]. Additionally, H19/miR-29b-3p/signal transducer and activator of the transcription 3 (STAT3) signaling pathway is also considered to be involved in cell proliferation, viability, apoptosis, and EMT of LAD Calu-3 and NCI-H1975 cell lines [55]. H19 also promotes NSCLC metastasis by activating some cellular signaling pathway proteins, including metastasis associated in colon cancer 1 (MACC1), epidermal growth factor receptor (EGFR), β-catenin, and extracellular-signal-regulated kinase 1/2 (ERK1/2) [46]. Overexpression of H19 promotes cell proliferation, migration, and invasion by upregulating the expression of EMT markers, including snail family transcriptional repressor 1 (SNAI1), N-cadherin, and Vimentin [23][45][46][48][56]. Moreover, upregulation of H19 can induce A549 cells resistance to DDP [56][57]. SNP rs2107425 in H19 is also reported to be associated with resistance to platinum-based chemotherapy in SCLC [51]. Oncogene c-Myc has been shown to be associated with H19 regulation in NSCLC [58]. c-Myc induces H19 expression and then downregulates miR-107 to promote mitotic progression of the NSCLC cell line [58]. The in vivo and in vitro experiments revealed that c-Myc can bind to the promoter of H19 and then activate its transcription [59]. Collectively, activation of H19 promotes the progression of LC and it could also serve as a serological biomarker in diagnosing LC. Further studies might concentrate on the role in cancer stemness. Particularly, how to repress the expression of H19 in LC tissues represents a novel strategy for treating LC.

2.3. Taurine Upregulated Gene 1 (TUG1)

TUG1 is a 7.1 kb intergenic lncRNA located on chromosome 22q12 [60][61][62]. TUG1 was firstly discovered to play a crucial role in mouse retinal development [60][61][63]. After that, TUG1 was found to have an important role in other cancers such as LC, HCC, BC, OC, GC, CRC, esophageal squamous cell carcinoma (ESCC), osteosarcoma, glioma, and bladder cancer [60][64].
TUG1 is upregulated in the majority of the above cancer tissues but downregulated in LSCC and LAD tissues [60][61][62][64][65][66], suggesting that it may have tissue-specific expression patterns and a role in different human tumors [22]. NSCLC patients with high expression of TUG1 have a better prognosis [60]. In support, lower expression of TUG1 is associated with larger tumor size, advanced tumor lymph node metastasis (TNM) stage, and poorer OS in NSCLC patients [62]. Moreover, univariate and multivariate analysis revealed that TUG1 can serve as an independent predictor for OS in NSCLC patients [62]. However, TUG1 is found to be upregulated in SCLC tissues compare with that in adjacent normal tissues and its upregulation is associated with poor prognosis [67]. An additional study also revealed that TUG1 is upregulated in LAD cells and serum samples, and a high level of TUG1 is positively correlated with tumor size, TNM stage, lymph node metastases, and distant metastasis [68].
TUG1 expression is induced by the wild-type p53 in three NSCLC cell lines (A549, SK-MES-1, and NCI-H1299), and TUG1 knockdown increases cell proliferation in vitro and in vivo [62][66]. Additionally, TUG1 can bind with PRC2 in the promotor region of Elav-like family member 1 (CELF1) to inhibit the expression of the genes involved in cell cycle [69]. Moreover, TUG1/PRC2 complex could also bind to the homeobox B7 (HOXB7) promoter and activate its expression, thereby activating the Akt and mitogen-activated protein kinase (MAPK) pathways in NSCLC tissues [62]. However, TUG1 knockdown significantly inhibits cell proliferation, migration, and invasion and promotes cell apoptosis and cell cycle arrest in three SCLC cell lines (NCI-H69, NCI-H446, NCIH69AR) by regulating LIMK2b (a splice variant of LIM-kinase 2) expression via binding with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) [67]. TUG1 can also induce SCLC cell resistance to chemotherapeutic drugs, including DDP, adriamycin (ADM), and vepeside (VP-16) in vitro and in vivo [67]. In general, TUG1 plays an important role in the development of LC. However, further studies are needed to clarify the distinct mechanisms of TUG1 in NSCLC and SCLC.

2.4. Maternally Expressed Gene 3 (MEG3)

MEG3 is 6.9 kb in length and acts as a tumor suppressor gene located on chromosome 14q32.2 within the DLK1-MEG3 locus [22][70][71]. MEG3 is expressed in many normal tissues and is considered to be involved in many cellular processes [72]. Compared with adjacent non-tumor lung tissues, MEG3 is significantly downregulated in NSCLC tissues [72]. A meta-analysis declared that overexpression of MEG3 exhibited better prognosis in NSCLC patients, suggesting that MEG3 could serve as a prognostic factor of NSCLC patients [73]. Additionally, the MEG3 rs4081134 SNP is strongly associated with LC susceptibility in the Chinese population [70]. Moreover, MEG3 is also considered to be inhibited in other cancers, including HCC, NB, glioma, meningioma, bladder cancer, and hematological malignancies [25][70][74][75].
MEG3 is significantly downregulated in LC cell lines A549 and HCC823 [76]. Upregulation of MEG3 inhibits the viability, proliferation, and autophagy in H292 and A549 cells [72][77]. Upregulation of MEG3 increases cell apoptosis by suppressing the expression of apoptosis inhibitory protein B-cell lymphoma-2 (Bcl-2) and promoting apoptosis-promoting factor BCL2 associated X (Bax) in A549 cells [76]. MEG3 overexpression suppresses cell proliferation and induces apoptosis by activating the expression of p53 in vitro [71][72]. The retinoblastoma tumor suppressor (pRb) pathway, which is important in regulating cell cycle progression and cell proliferation, is revealed to inhibit cell proliferation by activating MEG3 expression in A549 and SK-MES-1 in LC cells [78]. In addition, the MEG3/microRNA-7-5p/BRCA1 regulatory network is also verified to be essential in NSCLC [76].
The drug resistance to chemotherapy drug vincristine is negatively associated with the expression of MEG3 in vitro [77]. Upregulation of MEG3 improves the sensitivity of DDP-resistant NSCLC cells to DDP treatment via inhibiting cell proliferation and inducing cell apoptosis modulated by the miR-21-5p/SRY-box transcription factor 7 (SOX7) axis [79]. MEG3 knockdown could also induce DDP resistance in A549/DDP cells by activating the Wnt/β-catenin signaling pathway [80]. Overall, these findings suggest that MEG3 could repress the development of LC, and it may also act as a therapeutic target for LC. Further study is also needed to clarify the mechanism(s) of MEG3 repression in LC tissues.

2.5. Actin Filament Associated Protein 1 Antisense RNA 1 (AFAP1-AS1)

AFAP1-AS1 is a 6.8 kb antisense lncRNA, which is located on chromosome 4p16.1. AFAP1-AS1 is transcribed from AFAP1 in the antisense direction and can also affect the expression of AFAP1 [24]. AFAP1-AS1 plays an important role in the progression of LC and other cancers, including LC, HCC, GC, PC, CRC, OC, and gallbladder cancer (GBC) [24].
AFAP1-AS1 expression is positively correlated with tumor pathological grade, TNM staging, smoking history, infiltration degree, distant metastasis, and clinical outcomes in NSCLC patients [73][81][82][83]. High expression of AFAP1-AS1 is correlated with advanced lymph node metastasis and reduced survival time [84]. A meta-analysis report showed that increased expression level of AFAP1-AS1 is a strong predictor of poor OS in NSCLC patients [73]. These findings suggest that AFAP1-AS1 could serve as a prognostic biomarker for NSCLC.
AFAP1-AS1 is upregulated in NSCLC tissues and cell lines [73][81][82][83][84][85][86][87][88][89]. Inhibition of AFAP-AS1 suppresses cell growth and migration and promotes apoptosis of NSCLC cells in vitro [85][86]. AFAP1-AS1 knockdown leads to a significant increase in keratin 1 (KRT1) expression in vitro, suggesting that the oncogenic activity of AFAP1-AS1 is mediated by suppressing KRT1 expression [86]. Moreover, AFAP1-AS1 knockdown also inhibits tumor growth of LC in BALB/c nude mice [86]. In contrast, overexpression of AFAP1-AS1 promotes proliferation, migration, and invasion, and inhibits apoptosis of NSCLC cell lines by upregulating the interferon regulatory factor (IRF) 7 and retinoid-inducible protein (RIG)-I-like receptor signaling pathways [87]. AFAP-AS1 can also promote NSCLC cell growth by recruiting EZH2 to epigenetically downregulate p21 expression [83]. In general, AFAP-AS1 promotes LC cell proliferation and migration, and inhibits cell apoptosis via multiple signaling pathways.

References

  1. Ponting, C.P.; Oliver, P.L.; Reik, W. Evolution and Functions of Long Noncoding RNAs. Cell 2009, 136, 629–641.
  2. Hu, G.; Niu, F.; Humburg, B.A.; Liao, K.; Bendi, S.; Callen, S.; Fox, H.S.; Buch, S. Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis. Oncotarget 2018, 9, 18648–18663.
  3. Wang, K.C.; Chang, H.Y. Molecular mechanisms of long noncoding RNAs. Mol. Cell 2011, 43, 904–914.
  4. Akhade, V.S.; Pal, D.; Kanduri, C. Long Noncoding RNA: Genome Organization and Mechanism of Action. Adv. Exp. Med. Biol. 2017, 1008, 47–74.
  5. Deans, C.; Maggert, K.A. What Do You Mean, “Epigenetic”? Genetics 2015, 199, 887–896.
  6. Peterson, C.L.; Workman, J.L. Promoter targeting and chromatin remodeling by the SWI/SNF complex. Curr. Opin. Genet. Dev. 2000, 10, 187–192.
  7. Wu, Q.; Lian, J.B.; Stein, J.L.; Stein, G.S.; Nickerson, A.J.; Imbalzano, A.N. The BRG1 ATPase of human SWI/SNF chromatin remodeling enzymes as a driver of cancer. Epigenomics 2017, 9, 919–931.
  8. Tang, Y.; Wang, J.; Lian, Y.; Fan, C.; Zhang, P.; Wu, Y.; Li, X.; Xiong, F.; Li, X.; Li, G.; et al. Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer. Mol. Cancer 2017, 16, 42.
  9. Lee, R.S.; Roberts, C.W.M. Linking the SWI/SNF complex to prostate cancer. Nat. Genet. 2013, 45, 1268–1269.
  10. Chen, Z.; Gao, Y.; Yao, L.; Liu, Y.; Huang, L.; Yan, Z.; Zhao, W.; Zhu, P.; Weng, H. LncFZD6 initiates Wnt/β-catenin and liver TIC self-renewal through BRG1-mediated FZD6 transcriptional activation. Oncogene 2018, 37, 3098–3112.
  11. Wang, Y.; He, L.; Du, Y.; Zhu, P.; Huang, G.; Luo, J.; Yan, X.; Ye, B.; Li, C.; Xia, P.; et al. The Long Noncoding RNA lncTCF7 Promotes Self-Renewal of Human Liver Cancer Stem Cells through Activation of Wnt Signaling. Cell Stem Cell 2015, 16, 413–425.
  12. Deng, J.; Mueller, M.; Geng, T.; Shen, Y.; Liu, Y.; Hou, P.; Ramillapalli, R.; Taylor, H.S.; Paidas, M.; Huang, Y. H19 lncRNA alters methylation and expression of Hnf4α in the liver of metformin-exposed fetuses. Cell Death Dis. 2017, 8, e3175.
  13. Arab, K.; Park, Y.J.; Lindroth, A.M.; Schäfer, A.; Oakes, C.; Weichenhan, D.; Lukanova, A.; Lundin, E.; Risch, A.; Meister, M.; et al. Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A. Mol. Cell 2014, 55, 604–614.
  14. Jain, A.K.; Xi, Y.; McCarthy, R.; Allton, K.; Akdemir, K.C.; Patel, L.R.; Aronow, B.; Lin, C.; Li, W.; Yang, L.; et al. LncPRESS1 is a p53-regulated lncRNA that safeguards pluripotency by disrupting SIRT6 mediated de-acetylation of histone H3K56. Mol. Cell 2016, 64, 967–981.
  15. Xu, M.; Chen, X.; Lin, K.; Zeng, K.; Liu, X.; Pan, B.; Xu, X.; Xu, T.; Hu, X.; Sun, L.; et al. The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol. Cancer 2018, 17, 141.
  16. Terashima, M.; Tange, S.; Ishimura, A.; Suzuki, T. MEG3 Long Noncoding RNA Contributes to the Epigenetic Regulation of Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines. J. Biol. Chem. 2017, 292, 82–99.
  17. Chiu, H.S.; Llobet-Navas, D.; Yang, X.; Chung, W.J.; Ambesi-Impiombato, A.; Iyer, A.; Kim, H.R.; Seviour, E.G.; Luo, Z.; Sehgal, V.; et al. Cupid: Simultaneous reconstruction of microRNA-target and ceRNA networks. Genome Res. 2015, 25, 257–267.
  18. Thomson, D.W.; Dinger, M.E. Endogenous microRNA sponges: Evidence and controversy. Nat. Rev. Genet. 2016, 17, 272–283.
  19. Tam, C.; Wong, J.H.; Tsui, S.K.W.; Zuo, T.; Chan, T.F.; Ng, T.B. LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: Updates in recent years. Appl. Microbiol. Biotechnol. 2019, 103, 4649–4677.
  20. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 2018, 68, 394–424.
  21. Zhao, Y.; Feng, C.; Li, Y.; Ma, Y.; Cai, R. LncRNA H19 promotes lung cancer proliferation and metastasis by inhibiting miR-200a function. Mol. Cell. Biochem. 2019, 1–8.
  22. Xie, W.; Yuan, S.; Sun, Z.; Li, Y. Long noncoding and circular RNAs in lung cancer: Advances and perspectives. Epigenomics 2016, 8, 1275–1287.
  23. Qian, B.; Wang, D.M.; Gu, X.S.; Zhou, K.; Wu, J.; Zhang, C.Y.; He, X.Y. LncRNA H19 serves as a ceRNA and participates in non-small cell lung cancer development by regulating microRNA-107. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 5946–5953.
  24. Zhang, F.; Li, J.; Xiao, H.; Zou, Y.; Liu, Y.; Huang, W. AFAP1-AS1: A novel oncogenic long non-coding RNA in human cancers. Cell Prolif. 2018, 51.
  25. Guo, T.; Li, J.; Zhang, L.; Hou, W.; Wang, R.; Zhang, J.; Gao, P. Multidimensional communication of microRNAs and long non-coding RNAs in lung cancer. J. Cancer Res. Clin. Oncol. 2019, 145, 31–48.
  26. Sun, Y.; Ma, L. New Insights into Long Non-Coding RNA MALAT1 in Cancer and Metastasis. Cancers 2019, 11, 216.
  27. He, R.Z.; Luo, D.X.; Mo, Y.Y. Emerging roles of lncRNAs in the post-transcriptional regulation in cancer. Genes Dis. 2019, 6, 6–15.
  28. Bhan, A.; Soleimani, M.; Mandal, S.S. Long Noncoding RNA and Cancer: A New Paradigm. Cancer Res. 2017, 77, 3965–3981.
  29. Huang, J.L.; Liu, W.; Tian, L.H.; Chai, T.T.; Liu, Y.; Zhang, F.; Fu, H.Y.; Zhou, H.R.; Shen, J.Z. Upregulation of long non-coding RNA MALAT-1 confers poor prognosis and influences cell proliferation and apoptosis in acute monocytic leukemia. Oncol. Rep. 2017, 38, 1353–1362.
  30. Bi, S.; Wang, C.; Li, Y.; Zhang, W.; Zhang, J.; Lv, Z.; Wang, J. LncRNA-MALAT1-mediated Axl promotes cell invasion and migration in human neuroblastoma. Tumor Biol. 2017, 39, 1010428317699796.
  31. Lu, T.; Wang, Y.; Chen, D.; Liu, J.; Jiao, W. Potential clinical application of lncRNAs in non-small cell lung cancer. Onco Targets Ther. 2018, 11, 8045–8052.
  32. Gutschner, T.; Hammerle, M.; Eissmann, M.; Hsu, J.; Kim, Y.; Hung, G.; Revenko, A.; Arun, G.; Stentrup, M.; Gross, M.; et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013, 73, 1180–1189.
  33. Arun, G.; Diermeier, S.; Akerman, M.; Chang, K.-C.; Wilkinson, J.; Hearn, S.; Kim, Y.; MacLeod, A.; Krainer, A.R.; Norton, L.; et al. Abstract PR11: Differentiation of mammary tumors and reduction in metastasis upon Malat1 LncRNA loss. Mech. Noncoding RNAs Tumorigenesis 2016, 76, PR11.
  34. Guo, F.; Guo, L.; Li, Y.; Zhou, Q.; Li, Z. MALAT1 is an oncogenic long non-coding RNA associated with tumor invasion in non-small cell lung cancer regulated by DNA methylation. Int. J. Clin. Exp. Pathol. 2015, 8, 15903–15910.
  35. Chen, W.; Zhao, W.; Chen, S.; Zhang, L.; Guo, Z.; Wang, L.; Wang, J.; Wan, Z.; Hong, Y.; Yu, L. Expression and correlation of MALAT1 and SOX9 in non-small cell lung cancer. Clin. Respir. J. 2018, 12, 2284–2291.
  36. Dong, X.; Liu, M.; Sun, W.; Liu, Y. The role of lncRNA MALAT1 in bone metastasis in patients with non-small cell lung cancer. Oncol. Rep. 2016, 36, 1679–1685.
  37. Guo, F.; Yu, F.; Wang, J.; Li, Y.; Li, Y.; Li, Z.; Zhou, Q. Expression of MALAT1 in the peripheral whole blood of patients with lung cancer. Biomed. Rep. 2015, 3, 309–312.
  38. Weber, D.G.; Johnen, G.; Casjens, S.; Bryk, O.; Pesch, B.; Jockel, K.-H.; Kollmeier, J.; Brüning, T. Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res. Notes 2013, 6, 518.
  39. Li, S.; Mei, Z.; Zhang, X.; Hu, H.-B.; Hu, H. The lncRNA MALAT1 contributes to non-small cell lung cancer development via modulating miR-124/STAT3 axis. J. Cell. Physiol. 2018, 233, 6679–6688.
  40. Zhang, R.; Xia, Y.; Wang, Z.; Zheng, J.; Chen, Y.; Li, X.; Wang, Y.; Ming, H. Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer. Biochem. Biophys. Res. Commun. 2017, 490, 406–414.
  41. Tang, Y.; Xiao, G.; Chen, Y.; Deng, Y. LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling. Anti-Cancer Drugs 2018, 29, 725–735.
  42. Li, J.; Wang, J.; Chen, Y.; Li, S.; Jin, M.; Wang, H.; Chen, Z.; Yu, W. LncRNA MALAT1 exerts oncogenic functions in lung adenocarcinoma by targeting miR-204. Am. J. Cancer Res. 2016, 6, 1099–1107.
  43. Feng, C.; Zhao, Y.; Li, Y.; Zhang, T.; Ma, Y.; Liu, Y. LncRNA MALAT1 Promotes Lung Cancer Proliferation and Gefitinib Resistance by Acting as a miR-200a Sponge. Arch. Bronconeumol. 2019.
  44. Wang, H.; Wang, L.; Zhang, G.; Lu, C.; Chu, H.; Yang, R.; Zhao, G. MALAT1/miR-101-3p/MCL1 axis mediates cisplatin resistance in lung cancer. Oncotarget 2018, 9, 7501–7512.
  45. Liao, S.; Yu, C.; Liu, H.; Zhang, C.; Li, Y.; Zhong, X. Long non-coding RNA H19 promotes the proliferation and invasion of lung cancer cells and regulates the expression of E-cadherin, N-cadherin, and vimentin. Onco Targets Ther. 2019, 12, 4099–4107.
  46. Wang, L.; Sun, Y.; Yi, J.; Wang, X.; Liang, J.; Pan, Z.; Li, L.; Jiang, G. Targeting H19 by lentivirus-mediated RNA interference increases A549 cell migration and invasion. Exp. Lung Res. 2016, 42, 346–353.
  47. Hu, C.; Yang, T.; Pan, J.; Zhang, J.; Yang, J.; He, J.; Zou, Y. Associations between H19 polymorphisms and neuroblastoma risk in Chinese children. Biosci. Rep. 2019, 39.
  48. Ge, X.; Zheng, L.; Feng, Z.; Li, M.; Liu, L.; Zhao, Y.; Jiang, J. H19 contributes to poor clinical features in NSCLC patients and leads to enhanced invasion in A549 cells through regulating miRNA-203-mediated epithelial-mesenchymal transition. Oncol. Lett. 2018, 16, 4480–4488.
  49. Yin, Z.; Cui, Z.; Li, H.; Li, J.; Zhou, B. Polymorphisms in the H19 gene and the risk of lung Cancer among female never smokers in Shenyang, China. BMC Cancer 2018, 18, 893.
  50. Zhang, Y.; Luo, J.; Li, Q.; Pan, J.; Li, L.; Fang, L. Expression level of long noncoding RNA H19 in plasma of patients with nonsmall cell lung cancer and its clinical significance. J. Cancer Res. Ther. 2018, 14, 860.
  51. Gong, W.J.; Yin, J.Y.; Li, X.P.; Fang, C.; Xiao, D.; Zhang, W.; Zhou, H.H.; Li, X.; Liu, Z.Q. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumor Biol. 2016, 37, 8349–8358.
  52. Zhou, Y.; Sheng, B.; Xia, Q.; Guan, X.; Zhang, Y. Association of long non-coding RNA H19 and microRNA-21 expression with the biological features and prognosis of non-small cell lung cancer. Cancer Gene Ther. 2017, 24, 317–324.
  53. Ren, J.; Fu, J.; Ma, T.; Yan, B.; Gao, R.; An, Z.; Wang, D. LncRNA H19-elevated LIN28B promotes lung cancer progression through sequestering miR-196b. Cell Cycle 2018, 17, 1–9.
  54. Su, M.; Xiao, Y.; Tang, J.; Wu, J.; Ma, J.; Tian, B.; Zhou, Y.; Wang, H.; Yang, D.; Liao, Q.-J.; et al. Role of lncRNA and EZH2 Interaction/Regulatory Network in Lung Cancer. J. Cancer 2018, 9, 4156–4165.
  55. Liu, L.; Liu, L.; Lu, S. lncRNA H19 promotes viability and epithelial-mesenchymal transition of lung adenocarcinoma cells by targeting miR-29b-3p and modifying STAT3. Int. J. Oncol. 2019, 54, 929–941.
  56. Wang, Q.; Cheng, N.; Li, X.; Pan, H.; Li, C.; Ren, S.; Su, C.; Cai, W.; Zhao, C.; Zhang, L.; et al. Correlation of long non-coding RNA H19 expression with cisplatin-resistance and clinical outcome in lung adenocarcinoma. Oncotarget 2017, 8, 2558–2567.
  57. Peng, W.; Wang, J.; Shan, B.; Peng, Z.; Dong, Y.; Shi, W.; He, D.; Cheng, Y.; Zhao, W.; Zhang, C.; et al. Diagnostic and Prognostic Potential of Circulating Long Non-Coding RNAs in Non Small Cell Lung Cancer. Cell. Physiol. Biochem. 2018, 49, 816–827.
  58. Cui, J.; Mo, J.; Luo, M.; Yu, Q.; Zhou, S.; Li, T.; Zhang, Y.; Luo, W. c-Myc-activated long non-coding RNA H19 downregulates miR-107 and promotes cell cycle progression of non-small cell lung cancer. Int. J. Clin. Exp. Pathol. 2015, 8, 12400–12409.
  59. Barsyte-Lovejoy, D.; Lau, S.K.; Boutros, P.C.; Khosravi, F.; Jurisica, I.; Andrulis, I.L.; Tsao, M.S.; Penn, L.Z. The c-Myc Oncogene Directly Induces the H19 Noncoding RNA by Allele-Specific Binding to Potentiate Tumorigenesis. Cancer Res. 2006, 66, 5330–5337.
  60. Ma, P.J.; Guan, Q.K.; Meng, L.; Qin, N.; Zhao, J.; Jin, B.Z. Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: A meta-analysis. Oncotarget 2017, 8, 62454–62462.
  61. Ghaforui-Fard, S.; Vafaee, R.; Taheri, M. Taurine-upregulated gene 1: A functional long noncoding RNA in tumorigenesis. J. Cell. Physiol. 2019, 234, 17100–17112.
  62. Zhang, E.B.; Yin, D.D.; Sun, M.; Kong, R.; Liu, X.H.; You, L.H.; Han, L.; Xia, R.; Wang, K.M.; Yang, J.S.; et al. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis. 2014, 5, e1243.
  63. Zhang, E.; He, X.; Yin, D.; Han, L.; Qiu, M.; Xu, T.; Xia, R.; Xu, L.; Yin, R.; De, W. Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57. Cell Death Dis. 2016, 7, e2109.
  64. Li, Z.; Shen, J.; Chan, M.T.; Wu, W.K.K. TUG1: A pivotal oncogenic long non-coding RNA of human cancers. Cell Prolif. 2016, 49, 471–475.
  65. Esfandi, F.; Taheri, M.; Omrani, M.D.; Shadmehr, M.B.; Arsang-Jang, S.; Shams, R.; Ghafouri-Fard, S. Expression of long non-coding RNAs (lncRNAs) has been dysregulated in non-small cell lung cancer tissues. BMC Cancer 2019, 19, 222.
  66. Lin, P.C.; Huang, H.D.; Chang, C.C.; Chang, Y.S.; Yen, J.C.; Lee, C.C.; Chang, W.H.; Liu, T.C.; Chang, J.G. Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2. BMC Cancer 2016, 16, 583.
  67. Niu, Y.; Ma, F.; Huang, W.; Fang, S.; Li, M.; Wei, T.; Guo, L. Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2. Mol. Cancer 2017, 16, 5.
  68. Liu, H.; Zhou, G.; Fu, X.; Cui, H.; Pu, G.; Xiao, Y.; Sun, W.; Dong, X.; Zhang, L.; Cao, S.; et al. Long noncoding RNA TUG1 is a diagnostic factor in lung adenocarcinoma and suppresses apoptosis via epigenetic silencing of BAX. Oncotarget 2017, 8, 101899–101910.
  69. Khalil, A.M.; Guttman, M.; Huarte, M.; Garber, M.; Raj, A.; Morales, D.R.; Thomas, K.; Presser, A.; Bernstein, B.E.; Van Oudenaarden, A.; et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc. Natl. Acad. Sci. USA 2009, 106, 11667–11672.
  70. Yang, Z.; Li, H.; Li, J.; Lv, X.; Gao, M.; Bi, Y.; Zhang, Z.; Wang, S.; Li, S.; Li, N.; et al. Association Between Long Noncoding RNA MEG3 Polymorphisms and Lung Cancer Susceptibility in Chinese Northeast Population. DNA Cell Biol. 2018, 37, 812–820.
  71. Al-Rugeebah, A.; Alanazi, M.; Parine, N.R. MEG3: An Oncogenic Long Non-coding RNA in Different Cancers. Pathol. Oncol. Res. 2019, 25, 859–874.
  72. Lu, K.H.; Li, W.; Liu, X.H.; Sun, M.; Zhang, M.L.; Wu, W.Q.; Xie, W.P.; Hou, Y.Y. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer 2013, 13, 461.
  73. Wang, M.; Ma, X.; Zhu, C.; Guo, L.; Li, Q.; Liu, M.; Zhang, J. The prognostic value of long non coding RNAs in non small cell lung cancer: A meta-analysis. Oncotarget 2016, 7, 81292–81304.
  74. Yao, H.; Sun, P.; Duan, M.; Lin, L.; Pan, Y.; Wu, C.; Fu, X.; Wang, H.; Guo, L.; Jin, T.; et al. microRNA-22 can regulate expression of the long non-coding RNA MEG3 in acute myeloid leukemia. Oncotarget 2017, 8, 65211–65217.
  75. Tang, W.; Dong, K.; Li, K.; Dong, R.; Zheng, S. MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways. Sci. Rep. 2016, 6, 36268.
  76. Wu, J.L.; Meng, F.M.; Li, H.J. High expression of lncRNA MEG3 participates in non-small cell lung cancer by regulating microRNA-7-5p. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 5938–5945.
  77. Xia, H.; Qu, X.L.; Liu, L.Y.; Qian, D.H.; Jing, H.Y. LncRNA MEG3 promotes the sensitivity of vincristine by inhibiting autophagy in lung cancer chemotherapy. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 1020–1027.
  78. Kruer, T.L.; Dougherty, S.M.; Reynolds, L.; Long, E.; De Silva, T.; Lockwood, W.W.; Clem, B.F. Expression of the lncRNA Maternally Expressed Gene 3 (MEG3) Contributes to the Control of Lung Cancer Cell Proliferation by the Rb Pathway. PLoS ONE 2016, 11, e0166363.
  79. Wang, P.; Chen, D.; Ma, H.; Li, Y. LncRNA MEG3 enhances cisplatin sensitivity in non-small cell lung cancer by regulating miR-21-5p/SOX7 axis. OncoTargets Ther. 2017, 10, 5137–5149.
  80. Xia, Y.; He, Z.; Liu, B.; Wang, P.; Chen, Y. Downregulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/β-catenin signaling pathway. Mol. Med. Rep. 2015, 12, 4530–4537.
  81. Yu, H.; Xu, Q.; Liu, F.; Ye, X.; Wang, J.; Meng, X. Identification and Validation of Long Noncoding RNA Biomarkers in Human Non–Small-Cell Lung Carcinomas. J. Thorac. Oncol. 2015, 10, 645–654.
  82. Deng, J.; Liang, Y.; Liu, C.; He, S.; Wang, S. The up-regulation of long non-coding RNA AFAP1-AS1 is associated with the poor prognosis of NSCLC patients. Biomed. Pharmacother. 2015, 75, 8–11.
  83. Yin, D.; Lu, X.; Su, J.; He, X.; De, W.; Yang, J.; Li, W.; Han, L.; Zhang, E. Long noncoding RNA AFAP1-AS1 predicts a poor prognosis and regulates non-small cell lung cancer cell proliferation by epigenetically repressing p21 expression. Mol. Cancer 2018, 17, 92.
  84. Leng, X.; Ding, X.; Wang, S.; Fang, T.; Shen, W.; Xia, W.; You, R.; Xu, K.; Yin, R. Long noncoding RNA AFAP1-AS1 is upregulated in NSCLC and associated with lymph node metastasis and poor prognosis. Oncol. Lett. 2018, 16, 727–732.
  85. Yu, S.; Yang, D.; Ye, Y.; Liu, P.; Chen, Z.; Lei, T.; Pu, J.; Liu, L.; Wang, Z. Long noncoding RNA actin filament-associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine-specific demethylase 1 and repressing HMG box-containing protein 1 in non-small-cell lung cancer. Cancer Sci. 2019.
  86. Peng, B.; Liu, A.; Yu, X.; Xu, E.; Dai, J.; Li, M.; Yang, Q. Silencing of lncRNA AFAP1-AS1 suppressed lung cancer development by regulatory mechanism in cis and trans. Oncotarget 2017, 8, 93608–93623.
  87. Tang, X.D.; Zhang, D.D.; Jia, L.; Ji, W.; Zhao, Y.S. lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway. Cell. Physiol. Biochem. 2018, 50, 179–195.
  88. Zeng, Z.; Bo, H.; Gong, Z.; Lian, Y.; Li, X.; Li, X.; Zhang, W.; Deng, H.; Zhou, M.; Peng, S.; et al. AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis. Tumour. Biol. 2016, 37, 729–737.
  89. Sui, J.; Li, Y.H.; Zhang, Y.Q.; Shen, X.; Yao, W.Z.; Hong, W.W.; Li, C.Y.; Peng, H.; Liang, G.Y.; Yin, L.H.; et al. Integrated analysis of long non-coding RNA-associated ceRNA network reveals potential lncRNA biomarkers in human lung adenocarcinoma. Int. J. Oncol. 2016, 49, 2023–2036.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Weidong Yu
View Times: 492
Revisions: 2 times (View History)
Update Date: 23 Mar 2022
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback