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Tumor Biology
Published in: Tumor Biology 2/2016

01-02-2016 | Review

The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers

Authors: Chenhui Ma, Xuefei Shi, Qingqing Zhu, Qian Li, Yafang Liu, Yanwen Yao, Yong Song

Published in: Tumor Biology | Issue 2/2016

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Abstract

Long noncoding RNAs (lncRNAs), which refer to a group of RNAs with length more than 200 nucleotides and limited protein-coding potential, play a widespread role in regulating biological processes, such as cell differentiation, proliferation, apoptosis, and migration. LncRNAs are dysregulated in multiple cancers, playing an either oncogenic or tumor-suppressive role. LncRNA GAS5 is a recently identified tumor suppressor involved in several cancers, like breast cancer, prostate cancer, lung cancer, and colorectal cancer. The low-expression pattern confers tumor cells elevated capacity of proliferation and predicts poorer prognosis. Existing studies mirror that lncRNA GAS5 promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. In this review, we will summarize the current knowledge about this vital lncRNA, from its discovery, characteristics, and biological function to molecular mechanism in various neoplasms.
Literature
1.
Booton R, Lindsay MA. Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest. 2014;146(1):193–204.CrossRefPubMed
2.
Consortium TEP. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74.CrossRef
3.
4.
5.
6.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89.CrossRefPubMedPubMedCentral
7.
Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21(6):354–61.CrossRefPubMed
8.
9.
Shi X, Sun M, Wu Y, Yao Y, Liu H, Wu G, et al. Post-transcriptional regulation of long noncoding RNAs in cancer. Tumour Biol. 2015;36(2):503–13.CrossRefPubMed
10.
Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, et al. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.CrossRefPubMedPubMedCentral
11.
Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2015;54 Suppl 1:E1–E12.CrossRefPubMed
12.
Yacqub-Usman K, Pickard MR, Williams GT. Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells. Prostate. 2015;75(7):693–705.CrossRefPubMed
13.
Stahel RA, Weder W, Felip E. Malignant pleural mesothelioma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20 Suppl 4:73–5.PubMed
14.
Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54:787–93.CrossRefPubMed
15.
SMITH CM, STEITZ JA. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol. 1998;18(12):6897–909.CrossRefPubMedPubMedCentral
16.
Williams GT, Farzaneh F. Are snoRNAs and snoRNA host genes new players in cancer? Nat Rev Cancer. 2012;12(2):84–8.PubMed
17.
COCCIA EM, Cicala C, Charlesworth A, Ciccarelli C, Rossi GB, Philipson L, et al. Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development. Mol Cell Biol. 1992;12(8):3514–21.CrossRefPubMedPubMedCentral
18.
Mourtada-Maarabouni M, Hasan AM, Farzaneh F, Williams GT. Inhibition of human T-cell proliferation by mammalian target of rapamycin (mTOR) antagonists requires noncoding RNA growth-arrest-specific transcript 5 (GAS5). Mol Pharmaco. 2010;78(1):19–28.CrossRef
19.
Tani H, Torimura M, Akimitsu N. The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells. PLoS One. 2013;8(1):e55684.CrossRefPubMedPubMedCentral
20.
Meyuhas O. Synthesis of the translational apparatus is regulated at the translational level. Eur J Biochem. 2000;267(21):6321–30.CrossRefPubMed
21.
Tani H, Imamachi N, Salam KA, Mizutani R, Ijiri K, Irie T, et al. Identification of hundreds of novel UPF1 target transcripts by direct determination of whole transcriptome stability. RNA Biol. 2012;9(11):1370–9.
22.
Imamachi N. Up-frameshift protein 1 (UPF1): multitalented entertainer in RNA decay. Drug Discov Ther. 2012;6(2):55–61.PubMed
23.
Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet. 2004;36(10):1073–8.CrossRefPubMed
24.
Isken O, Maquat LE. Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev. 2007;21(15):1833–56.CrossRefPubMed
25.
Mourtada-Maarabouni M, Hedge VL, Kirkham L, Farzaneh F, Williams GT. Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5). J Cell Sci. 2008;121(Pt 7):939–46.CrossRefPubMed
26.
Nakamura Y, Takahashi N, Kakegawa E, Yoshida K, Ito Y, Kayano H, et al. The GAS5 (growth arrest-specific transcript 5) gene fuses to BCL6 as a result of t(1;3)(q25;q27) in a patient with B-cell lymphoma. Cancer Genet Cytogenet. 2008;182(2):144–9.CrossRefPubMed
27.
Yin D, He X, Zhang E, Kong R, De W, Zhang Z. Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol. 2014;31(11):253.CrossRefPubMed
28.
Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208.CrossRefPubMed
29.
Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8.PubMedPubMedCentral
30.
Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, et al. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ. 2013;20(11):1558–68.CrossRefPubMedPubMedCentral
31.
Zhao X, Wang P, Liu J, Zheng J, Liu Y, Chen J, et al. Gas5 exerts tumor-suppressive functions in human glioma cells by targeting miR-222. Mol Ther. 2015. doi:10.​1038/​mt.​2015.​170
32.
Hu G, Lou Z, Gupta M. The long non-coding RNA GAS5 cooperates with the eukaryotic translation initiation factor 4E to regulate c-Myc translation. PLoS One. 2014;9(9):e107016.CrossRefPubMedPubMedCentral
33.
Liu Y, Zhao J, Zhang W, Gan J, Hu C, Huang G, et al. LncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer. Sci Rep. 2015;5:10159.CrossRefPubMedPubMedCentral
34.
Hajjari M, Salavaty A. HOTAIR: an oncogenic long non-coding RNA in different cancers. Cancer Biol Med. 2015;12(1):1–9.PubMedPubMedCentral
35.
Wu Y, Zhang L, Wang Y, Li H, Ren X, Wei F, et al. Long noncoding RNA HOTAIR involvement in cancer. Tumour Biol. 2014;35(10):9531–8.CrossRefPubMed
36.
Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, et al. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene. 2014;34(23):3076–84.CrossRefPubMed
37.
Li S, Wang Q, Qiang Q, Shan H, Shi M, Chen B, et al. Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor. J Cancer Res Clin Oncol. 2015;141(11):1909–20.CrossRefPubMed
38.
Pickard MR, Williams GT. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat. 2014;145(2):359–70.CrossRefPubMed
39.
Tamburrino L, Salvianti F, Marchiani S, Pinzani P, Nesi G, Serni S, et al. Androgen receptor (AR) expression in prostate cancer and progression of the tumor: Lessons from cell lines, animal models and human specimens. Steroids. 2012;77(10):996–1001.CrossRefPubMed
40.
Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 2013;1832(10):1613–23.CrossRefPubMed
41.
Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4(1):36–54.PubMedPubMedCentral
42.
Perez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, et al. Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. J Clin Oncol. 2004;22(16):3238–47.CrossRefPubMed
43.
44.
Svoboda M, Slyskova J, Schneiderova M, Makovicky P, Bielik L, Levy M, et al. HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis. 2014;35(7):1510–5.CrossRefPubMed
45.
Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 2014;25(5):666–81.
46.
Ling H, Vincent K, Pichler M, Fodde R, Berindan-Neagoe I, Slack FJ, et al. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene. 2015;34(39):5003–11.CrossRefPubMedPubMedCentral
47.
Tsang WP, Wong TW, Cheung AH, Co CN, Kwok TT. Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR. RNA. 2007;13(6):890–8.CrossRefPubMedPubMedCentral
48.
Jiang M, Huang O, Xie Z, Wu S, Zhang X, Shen A, et al. A novel long non-coding RNA-ARA: adriamycin resistance-associated. Biochem Pharmacol. 2014;87(2):254–83.CrossRefPubMed
49.
Yang Y, Li H, Hou S, Hu B, Liu J, Wang J. The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 2013;8(5):e65309.CrossRefPubMedPubMedCentral
50.
Cheng N, Li X, Zhao C, Ren S, Chen X, Cai W, et al. Microarray expression profile of long non-coding RNAs in EGFR-TKIs resistance of human non-small cell lung cancer. Oncol Rep. 2015;33(2):833–9.PubMed
51.
Dong S, Qu X, Li W, Zhong X, Li P, Yang S, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol. 2015;8(1):43.CrossRefPubMedPubMedCentral
52.
Wright CM, Kirschner MB, Cheng YY, O’Byrne KJ, Gray SG, Schelch K, et al. Long non coding RNAs (lncRNAs) are dysregulated in malignant pleural mesothelioma (MPM). PLoS One. 2013;8:e70940.CrossRefPubMedPubMedCentral
53.
Renganathan A, Kresoja-Rakic J, Echeverry N, Ziltener G, Vrugt B, Opitz I, et al. GAS5 long non-coding RNA in malignant pleural mesothelioma. Mol Cancer. 2014;13:119.CrossRefPubMedPubMedCentral
54.
Lu X, Fang Y, Wang Z, Xie J, Zhan Q, Deng X, et al. Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6. Cell Tissue Res. 2013;354(3):891–6.CrossRefPubMed
55.
Liu Z, Wang W, Jiang J, Bao E, Xu D, Zeng Y, et al. Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6. PLoS ONE. 2013;8(9):e73991.CrossRefPubMedPubMedCentral
56.
Qiao HP, Gao WS, Huo JX, Yang ZS. Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev. 2013;14(2):1077–82.CrossRefPubMed
57.
Tu ZQ, Li RJ, Mei JZ, Li XH. Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol. 2014;7(7):4303–9.PubMedPubMedCentral
58.
Cao S, Liu W, Li F, Zhao W, Qin C. Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol. 2014;7(10):6776–83.PubMedPubMedCentral
59.
Dufour M, Dormond-Meuwly A, Demartines N, Dormond O. Targeting the mammalian target of rapamycin (mTOR) in cancer therapy: lessons from past and future perspectives. Cancers (Basel). 2011;3(2):2478–500.CrossRef
60.
Zaytseva YY, Valentino JD, Gulhati P, Evers BM. mTOR inhibitors in cancer therapy. Cancer Lett. 2012;319(1):1–7.CrossRefPubMed
61.
Gezer U, Özgür E, Cetinkaya M, Isin M, Dalay N. Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int. 2014;38(9):1076–9.PubMed
Metadata
Title
The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers
Authors
Chenhui Ma
Xuefei Shi
Qingqing Zhu
Qian Li
Yafang Liu
Yanwen Yao
Yong Song
Publication date
01-02-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4521-9

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