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Published in: Pathology & Oncology Research 3/2019

01-07-2019 | Retinoblastoma | Review

MEG3: an Oncogenic Long Non-coding RNA in Different Cancers

Authors: Arwa Al-Rugeebah, Mohammed Alanazi, Narasimha Reddy Parine

Published in: Pathology & Oncology Research | Issue 3/2019

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Abstract

Long noncoding RNAs (lncRNAs) have recently considered as central regulators in diverse biological processes and emerged as vital players controlling tumorigenesis. Several lncRNAs can be classified into oncogenes and tumor suppressor genes depending on their function in cancer. A maternally expressed gene 3 (MEG3) gene transcripts a 1.6 kb lncRNA whose act as an antitumor component in different cancer cells, such as breast, liver, glioma, colorectal, cervical, gastric, lung, ovarian and osteosarcoma cancer cells. The present review highlights biological function of MEG3 to repress tumor through regulating the major tumor suppressor genes p53 and Rb, inhibiting angiogenesis-related factor, or controlling miRNAs. On the other hand, previous studies have also suggested that MEG3 mediates epithelial-mesenchymal transition (EMT). However, deregulation of MEG3 is associated with the  development and progression of cancer, suggesting that MEG3 may function as a potential biomarker and therapeutic target for human cancers.
Literature
1.
go back to reference Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, Laxman B, Asangani IA, Grasso CS, Kominsky HD, Cao X, Jing X, Wang X, Siddiqui J, Wei JT, Robinson D, Iyer HK, Palanisamy N, Maher CA, Chinnaiyan AM (2011) Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol 29(8):742–749. https://doi.org/10.1038/nbt.1914 CrossRefPubMedPubMedCentral Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, Laxman B, Asangani IA, Grasso CS, Kominsky HD, Cao X, Jing X, Wang X, Siddiqui J, Wei JT, Robinson D, Iyer HK, Palanisamy N, Maher CA, Chinnaiyan AM (2011) Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol 29(8):742–749. https://​doi.​org/​10.​1038/​nbt.​1914 CrossRefPubMedPubMedCentral
2.
go back to reference Ren S, Peng Z, Mao JH, Yu Y, Yin C, Gao X, Cui Z, Zhang J, Yi K, Xu W, Chen C, Wang F, Guo X, Lu J, Yang J, Wei M, Tian Z, Guan Y, Tang L, Xu C, Wang L, Gao X, Tian W, Wang J, Yang H, Wang J, Sun Y (2012) RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings. Cell Res 22(5):806–821. https://doi.org/10.1038/cr.2012.30 CrossRefPubMedPubMedCentral Ren S, Peng Z, Mao JH, Yu Y, Yin C, Gao X, Cui Z, Zhang J, Yi K, Xu W, Chen C, Wang F, Guo X, Lu J, Yang J, Wei M, Tian Z, Guan Y, Tang L, Xu C, Wang L, Gao X, Tian W, Wang J, Yang H, Wang J, Sun Y (2012) RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings. Cell Res 22(5):806–821. https://​doi.​org/​10.​1038/​cr.​2012.​30 CrossRefPubMedPubMedCentral
6.
go back to reference Brunner AL, Beck AH, Edris B, Sweeney RT, Zhu SX, Li R, Montgomery K, Varma S, Gilks T, Guo X, Foley JW, Witten DM, Giacomini CP, Flynn RA, Pollack JR, Tibshirani R, Chang HY, van de Rijn M, West RB (2012) Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol 13(8):R75. https://doi.org/10.1186/gb-2012-13-8-r75 CrossRefPubMedPubMedCentral Brunner AL, Beck AH, Edris B, Sweeney RT, Zhu SX, Li R, Montgomery K, Varma S, Gilks T, Guo X, Foley JW, Witten DM, Giacomini CP, Flynn RA, Pollack JR, Tibshirani R, Chang HY, van de Rijn M, West RB (2012) Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol 13(8):R75. https://​doi.​org/​10.​1186/​gb-2012-13-8-r75 CrossRefPubMedPubMedCentral
10.
go back to reference Wylie AA, Murphy SK, Orton TC, Jirtle RL (2000) Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. Genome Res 10(11):1711–1718CrossRefPubMedPubMedCentral Wylie AA, Murphy SK, Orton TC, Jirtle RL (2000) Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. Genome Res 10(11):1711–1718CrossRefPubMedPubMedCentral
12.
go back to reference Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F (2000) Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells 5(3):211–220CrossRefPubMed Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F (2000) Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells 5(3):211–220CrossRefPubMed
42.
43.
46.
go back to reference Wang P, Chen D, Ma H, Li Y (2017) Long non-coding RNA MEG3 regulates proliferation and apoptosis in non-small cell lung cancer via the miR-205-5p/LRP1 pathway. RSC Adv 7(78):49710–49719CrossRef Wang P, Chen D, Ma H, Li Y (2017) Long non-coding RNA MEG3 regulates proliferation and apoptosis in non-small cell lung cancer via the miR-205-5p/LRP1 pathway. RSC Adv 7(78):49710–49719CrossRef
54.
go back to reference Li CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, Lin P, Dewhirst MW (2000) Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst 92(2):143–147CrossRefPubMed Li CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, Lin P, Dewhirst MW (2000) Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst 92(2):143–147CrossRefPubMed
68.
go back to reference Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A (2008) Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 93(10):4119–4125. https://doi.org/10.1210/jc.2007-2633 CrossRefPubMedPubMedCentral Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A (2008) Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 93(10):4119–4125. https://​doi.​org/​10.​1210/​jc.​2007-2633 CrossRefPubMedPubMedCentral
69.
go back to reference Liu X, Gao Q, Li P, Zhao Q, Zhang J, Li J, Koseki H, Wong J (2013) UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9. Nat Commun 4:1563CrossRefPubMed Liu X, Gao Q, Li P, Zhao Q, Zhang J, Li J, Koseki H, Wong J (2013) UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9. Nat Commun 4:1563CrossRefPubMed
79.
go back to reference Padua Alves C, Fonseca AS, Muys BR, de Barros ELBR, Burger MC, de Souza JE, Valente V, Zago MA, Silva WA Jr (2013) Brief report: the lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells 31(12):2827–2832. https://doi.org/10.1002/stem.1547 CrossRefPubMed Padua Alves C, Fonseca AS, Muys BR, de Barros ELBR, Burger MC, de Souza JE, Valente V, Zago MA, Silva WA Jr (2013) Brief report: the lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells 31(12):2827–2832. https://​doi.​org/​10.​1002/​stem.​1547 CrossRefPubMed
83.
86.
go back to reference Zhang JJ, Guo SH, Jia BQ (2016) Down-regulation of long non-coding RNA MEG3 serves as an unfavorable risk factor for survival of patients with breast cancer. Eur Rev Med Pharmacol Sci 20(24):5143–5147PubMed Zhang JJ, Guo SH, Jia BQ (2016) Down-regulation of long non-coding RNA MEG3 serves as an unfavorable risk factor for survival of patients with breast cancer. Eur Rev Med Pharmacol Sci 20(24):5143–5147PubMed
89.
go back to reference Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, Mitra S, Mohammed A, James AR, Hoberg E, Moustakas A, Gyllensten U, Jones SJ, Gustafsson CM, Sims AH, Westerlund F, Gorab E, Kanduri C (2015) MEG3 long noncoding RNA regulates the TGF-beta pathway genes through formation of RNA-DNA triplex structures. Nat Commun 6:7743. https://doi.org/10.1038/ncomms8743 CrossRefPubMed Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, Mitra S, Mohammed A, James AR, Hoberg E, Moustakas A, Gyllensten U, Jones SJ, Gustafsson CM, Sims AH, Westerlund F, Gorab E, Kanduri C (2015) MEG3 long noncoding RNA regulates the TGF-beta pathway genes through formation of RNA-DNA triplex structures. Nat Commun 6:7743. https://​doi.​org/​10.​1038/​ncomms8743 CrossRefPubMed
96.
go back to reference Zheng Q, Lin Z, Xu J, Lu Y, Meng Q, Wang C, Yang Y, Xin X, Li X, Pu H (2018) Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN. Cell Death Dis 9(3):253CrossRefPubMedPubMedCentral Zheng Q, Lin Z, Xu J, Lu Y, Meng Q, Wang C, Yang Y, Xin X, Li X, Pu H (2018) Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN. Cell Death Dis 9(3):253CrossRefPubMedPubMedCentral
113.
go back to reference Qi P, Xu MD, Ni SJ, Shen XH, Wei P, Huang D, Tan C, Sheng WQ, Zhou XY, Du X (2015) Down-regulation of ncRAN, a long non-coding RNA, contributes to colorectal cancer cell migration and invasion and predicts poor overall survival for colorectal cancer patients. Mol Carcinog 54(9):742–750. https://doi.org/10.1002/mc.22137 CrossRefPubMed Qi P, Xu MD, Ni SJ, Shen XH, Wei P, Huang D, Tan C, Sheng WQ, Zhou XY, Du X (2015) Down-regulation of ncRAN, a long non-coding RNA, contributes to colorectal cancer cell migration and invasion and predicts poor overall survival for colorectal cancer patients. Mol Carcinog 54(9):742–750. https://​doi.​org/​10.​1002/​mc.​22137 CrossRefPubMed
121.
go back to reference Cao S, Liu W, Li F, Zhao W, Qin C (2014) Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol 7(10):6776–6783PubMedPubMedCentral Cao S, Liu W, Li F, Zhao W, Qin C (2014) Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol 7(10):6776–6783PubMedPubMedCentral
123.
go back to reference Jiang S, Wang HL, Yang J (2015) Low expression of long non-coding RNA LET inhibits carcinogenesis of cervical cancer. Int J Clin Exp Pathol 8(1):806–811PubMedPubMedCentral Jiang S, Wang HL, Yang J (2015) Low expression of long non-coding RNA LET inhibits carcinogenesis of cervical cancer. Int J Clin Exp Pathol 8(1):806–811PubMedPubMedCentral
125.
go back to reference Qin R, Chen Z, Ding Y, Hao J, Hu J, Guo F (2013) Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma 60(5):486–492CrossRefPubMed Qin R, Chen Z, Ding Y, Hao J, Hu J, Guo F (2013) Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma 60(5):486–492CrossRefPubMed
133.
go back to reference Sun TT, He J, Liang Q, Ren LL, Yan TT, Yu TC, Tang JY, Bao YJ, Hu Y, Lin Y, Sun D, Chen YX, Hong J, Chen H, Zou W, Fang JY (2016) LncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern. Cancer Discov 6(7):784–801. https://doi.org/10.1158/2159-8290.CD-15-0921 CrossRefPubMed Sun TT, He J, Liang Q, Ren LL, Yan TT, Yu TC, Tang JY, Bao YJ, Hu Y, Lin Y, Sun D, Chen YX, Hong J, Chen H, Zou W, Fang JY (2016) LncRNA GClnc1 promotes gastric carcinogenesis and may act as a modular scaffold of WDR5 and KAT2A complexes to specify the histone modification pattern. Cancer Discov 6(7):784–801. https://​doi.​org/​10.​1158/​2159-8290.​CD-15-0921 CrossRefPubMed
137.
go back to reference Wei GH, Wang X (2017) lncRNA MEG3 inhibit proliferation and metastasis of gastric cancer via p53 signaling pathway. Eur Rev Med Pharmacol Sci 21(17):3850–3856PubMed Wei GH, Wang X (2017) lncRNA MEG3 inhibit proliferation and metastasis of gastric cancer via p53 signaling pathway. Eur Rev Med Pharmacol Sci 21(17):3850–3856PubMed
143.
go back to reference Whiteside EJ, Seim I, Pauli JP, O'Keeffe AJ, Thomas PB, Carter SL, Walpole CM, Fung JN, Josh P, Herington AC, Chopin LK (2013) Identification of a long non-coding RNA gene, growth hormone secretagogue receptor opposite strand, which stimulates cell migration in non-small cell lung cancer cell lines. Int J Oncol 43(2):566–574. https://doi.org/10.3892/ijo.2013.1969 CrossRefPubMed Whiteside EJ, Seim I, Pauli JP, O'Keeffe AJ, Thomas PB, Carter SL, Walpole CM, Fung JN, Josh P, Herington AC, Chopin LK (2013) Identification of a long non-coding RNA gene, growth hormone secretagogue receptor opposite strand, which stimulates cell migration in non-small cell lung cancer cell lines. Int J Oncol 43(2):566–574. https://​doi.​org/​10.​3892/​ijo.​2013.​1969 CrossRefPubMed
156.
157.
go back to reference Hu X, Feng Y, Zhang D, Zhao SD, Hu Z, Greshock J, Zhang Y, Yang L, Zhong X, Wang LP, Jean S, Li C, Huang Q, Katsaros D, Montone KT, Tanyi JL, Lu Y, Boyd J, Nathanson KL, Li H, Mills GB, Zhang L (2014) A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. Cancer Cell 26(3):344–357. https://doi.org/10.1016/j.ccr.2014.07.009 CrossRefPubMedPubMedCentral Hu X, Feng Y, Zhang D, Zhao SD, Hu Z, Greshock J, Zhang Y, Yang L, Zhong X, Wang LP, Jean S, Li C, Huang Q, Katsaros D, Montone KT, Tanyi JL, Lu Y, Boyd J, Nathanson KL, Li H, Mills GB, Zhang L (2014) A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. Cancer Cell 26(3):344–357. https://​doi.​org/​10.​1016/​j.​ccr.​2014.​07.​009 CrossRefPubMedPubMedCentral
167.
go back to reference Tian ZZ, Guo XJ, Zhao YM, Fang Y (2015) Decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma. Int J Clin Exp Pathol 8(11):15138–15142PubMedPubMedCentral Tian ZZ, Guo XJ, Zhao YM, Fang Y (2015) Decreased expression of long non-coding RNA MEG3 acts as a potential predictor biomarker in progression and poor prognosis of osteosarcoma. Int J Clin Exp Pathol 8(11):15138–15142PubMedPubMedCentral
177.
go back to reference Guo W, Dong Z, Liu S, Qiao Y, Kuang G, Guo Y, Shen S, Liang J (2017) Promoter hypermethylation-mediated downregulation of miR-770 and its host gene MEG3, a long non-coding RNA, in the development of gastric cardia adenocarcinoma. Mol Carcinog 56(8):1924–1934. https://doi.org/10.1002/mc.22650 CrossRefPubMed Guo W, Dong Z, Liu S, Qiao Y, Kuang G, Guo Y, Shen S, Liang J (2017) Promoter hypermethylation-mediated downregulation of miR-770 and its host gene MEG3, a long non-coding RNA, in the development of gastric cardia adenocarcinoma. Mol Carcinog 56(8):1924–1934. https://​doi.​org/​10.​1002/​mc.​22650 CrossRefPubMed
Metadata
Title
MEG3: an Oncogenic Long Non-coding RNA in Different Cancers
Authors
Arwa Al-Rugeebah
Mohammed Alanazi
Narasimha Reddy Parine
Publication date
01-07-2019
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 3/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00614-3

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