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01-11-2014 | Original Paper

Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer

Authors: Dandan Yin, Xuezhi He, Erbao Zhang, Rong Kong, Wei De, Zhihong Zhang

Published in: Medical Oncology | Issue 11/2014

Abstract

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Recent studies have shown that lncRNAs play important roles in carcinogenesis. The aim of this study was to explore the role of lncRNA GAS5 in CRC. Real-time PCR was performed to investigate the expression of GAS5 in tumor tissues and corresponding non-tumor colorectal tissues from 66 patients with CRC. The lower expression of GAS5 was significantly correlated with large tumor size, low histological grade and advanced TNM stage. Multivariate analyses revealed that GAS5 expression served as an independent predictor for overall survival (P = 0.034). Further experiments revealed that overexpressed GAS5 significantly repressed the proliferation both in vitro and in vivo. In conclusion, our results suggest that GAS5, as a growth regulator, may serve as a candidate prognostic biomarker in human colorectal cancer.

Reissfelder C, Timke C, Schmitz-Winnenthal H, Rahbari NN, Koch M, Klug F, Roeder F, Edler L, Debus J, Buchler MW, et al. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer. BMC Cancer. 2011;11:419.PubMedCrossRefPubMedCentral

Reissfelder C, Rahbari NN, Koch M, Ulrich A, Pfeilschifter I, Waltert A, Muller SA, Schemmer P, Buchler MW, Weitz J. Validation of prognostic scoring systems for patients undergoing resection of colorectal cancer liver metastases. Ann Surg Oncol. 2009;16(12):3279–88.PubMedCrossRef

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.PubMedCrossRef

Rupnarain C, Dlamini Z, Naicker S, Bhoola K. Colon cancer: genomics and apoptotic events. Biol Chem. 2004;385(6):449–64.PubMedCrossRef

Calvert PM, Frucht H. The genetics of colorectal cancer. Ann Intern Med. 2002;137(7):603–12.PubMedCrossRef

Spizzo R, Almeida MI, Colombatti A, Calin GA. Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene. 2012;31(43):4577–87.PubMedCrossRefPubMedCentral

Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011;54(5):1679–89.PubMedCrossRef

Cui Z, Ren S, Lu J, Wang F, Xu W, Sun Y, Wei M, Chen J, Gao X, Xu C, et al. The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor. Urol Oncol. 2013;31(7):1117–23.PubMedCrossRef

Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.PubMedCrossRef

10.

Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, Song Y. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2013.

11.

Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP, Hou YY. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 2013;13:461.PubMedCrossRefPubMedCentral

12.

Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, Xu TP, Xia R, Yang JS, De W, et al. Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget. 2014;5(8):2276–92.PubMedPubMedCentral

13.

Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, 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.PubMedCrossRefPubMedCentral

14.

Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.PubMedCrossRefPubMedCentral

15.

Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32(13):1616–25.PubMedCrossRefPubMedCentral

16.

Zhou Y, Zhang X, Klibanski A. MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol. 2012;48(3):R45–53.PubMedCrossRefPubMedCentral

17.

Benetatos L, Vartholomatos G, Hatzimichael E. MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer. 2011;129(4):773–9.PubMedCrossRef

18.

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

19.

Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54(6):787–93.PubMedCrossRef

20.

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.PubMedCrossRef

21.

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.PubMedCrossRef

22.

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.PubMedCrossRef

23.

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.PubMedCrossRef

24.

Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816.PubMedCrossRef

25.

Louro R, Smirnova AS, Verjovski-Almeida S. Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics. 2009;93(4):291–8.PubMedCrossRef

26.

Amaral PP, Dinger ME, Mercer TR, Mattick JS. The eukaryotic genome as an RNA machine. Science. 2008;319(5871):1787–9.PubMedCrossRef

27.

Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009;458(7235):223–7.PubMedCrossRefPubMedCentral

28.

Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res. 2014;114(9):1389–97.PubMedCrossRef

29.

30.

Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol BioSyst. 2012;8(9):2289–94.PubMedCrossRef

31.

Nie L, Wu HJ, Hsu JM, Chang SS, Labaff AM, Li CW, Wang Y, Hsu JL, Hung MC. Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer. Am J Transl Res. 2012;4(2):127–50.PubMedPubMedCentral

32.

Prensner JR, Rubin MA, Wei JT, Chinnaiyan AM. Beyond PSA: the next generation of prostate cancer biomarkers. Sci Transl Med. 2012;4(127):127rv123.CrossRef

33.

Salagierski M, Schalken JA. Molecular diagnosis of prostate cancer: pCA3 and TMPRSS2:ERG gene fusion. J Urol. 2012;187(3):795–801.PubMedCrossRef

34.

Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, Zheng SS. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18(5):1243–50.PubMedCrossRef

35.

Garcia-Claver A, Lorente M, Mur P, Campos-Martin Y, Mollejo M, Velasco G, Melendez B. Gene expression changes associated with erlotinib response in glioma cell lines. Eur J Cancer. 2013;49(7):1641–53.PubMedCrossRef

36.

Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, Liu YW, Zhang EB, Liu XH, De W. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.PubMedCrossRefPubMedCentral

37.

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

38.

Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, Wu F, Mo YY. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ. 2013;20(11):1558–68.PubMedCrossRef

Title: Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer
Authors: Dandan Yin
Xuezhi He
Erbao Zhang
Rong Kong
Wei De
Zhihong Zhang
Publication date: 01-11-2014
Publisher: Springer US
Published in: Medical Oncology / Issue 11/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-014-0253-8

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