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Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6

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Abstract

Recent studies have revealed that long non-coding RNAs (lncRNAs) play important roles in cancer biology and that lncRNA gas5 (growth arrest-specific 5) regulates breast cancer cell growth. However, the role of gas5 in pancreatic cancer progression remains largely unknown. In the current study, we assay the expression level of gas5 in pancreatic cancer tissues and define the role of gas5 in the regulation of pancreatic cancer cell proliferation. We verify that the expression level of gas5 is significantly decreased in pancreatic cancer tissues compared with normal control. Overexpression of gas5 in pancreatic cancer cells inhibits cell proliferation, whereas gas5 inhibition induces a significant decrease in G0/G1 phase and an increase in S phase. We further demonstrate that gas5 negatively regulates CDK6 (cyclin-dependent kinase 6) expression in vitro and in vivo. More importantly, knockdown of CDK6 partially abrogates gas5-siRNA-induced cell proliferation. These data suggest an important role of gas5 in the molecular etiology of pancreatic cancer and implicate the potential application of gas5 in pancreatic cancer therapy.

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References

  • Chen Z, Chen LY, Dai HY, Wang P, Gao S, Wang K (2012) miR-301a promotes pancreatic cancer cell proliferation by directly inhibiting Bim expression. J Cell Biochem 113:3229–3235

    Article  PubMed  CAS  Google Scholar 

  • Chen ZK, Lin LW, Weng XH, Xue ES, Lin YH (2009) Interstitial chemotherapy with ricin-loaded thermosensitive hydrogel in pancreatic cancer xenograft. Hepatobiliary Pancreat Dis Int 8:418–423

    PubMed  CAS  Google Scholar 

  • Coccia EM, Cicala C, Charlesworth A, Ciccarelli C, Rossi GB, Philipson L, Sorrentino V (1992) Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development. Mol Cell Biol 12:3514–3521

    PubMed  CAS  Google Scholar 

  • Gibb EA, Brown CJ, Lam WL (2011) The functional role of long non-coding RNA in human carcinomas. Mol Cancer 10:38

    Article  PubMed  CAS  Google Scholar 

  • Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    Article  PubMed  CAS  Google Scholar 

  • Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM (2010) miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem 285:25221–25231

    Article  PubMed  CAS  Google Scholar 

  • Kapranov P, Willingham AT, Gingeras TR (2007) Genome-wide transcription and the implications for genomic organization. Nat Rev Genet 8:413–423

    Article  PubMed  CAS  Google Scholar 

  • Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP (2010) Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal 3:ra8

    Article  PubMed  Google Scholar 

  • Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, Miyano S, Mori M (2011) Long non-coding RNA HOTAIR regulates Polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71:6320–6326

    Google Scholar 

  • Lebedeva IV, Sarkar D, Su ZZ, Gopalkrishnan RV, Athar M, Randolph A, Valerie K, Dent P, Fisher PB (2006) Molecular target-based therapy of pancreatic cancer. Cancer Res 66:2403–2413

    Article  PubMed  CAS  Google Scholar 

  • Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J (2013a) Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett 333:213–221

    Article  PubMed  CAS  Google Scholar 

  • Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J (2013b) Upregulated H19 contributes to bladder cancer cell proliferation by regulating ID2 expression. FEBS J 280:1709–1716

    Article  PubMed  CAS  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    Article  PubMed  CAS  Google Scholar 

  • Mourtada-Maarabouni M, Hedge VL, Kirkham L, Farzaneh F, Williams GT (2008) Growth arrest in human T-cells is controlled by the non-coding RNA growth-arrest-specific transcript 5 (GAS5). J Cell Sci 121:939–946

    Article  PubMed  CAS  Google Scholar 

  • Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT (2009) GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene 28:195–208

    Article  PubMed  CAS  Google Scholar 

  • Sana J, Faltejskova P, Svoboda M, Slaby O (2012) Novel classes of non-coding RNAs and cancer. J Transl Med 10:103

    Article  PubMed  CAS  Google Scholar 

  • Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008) Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett 582:1564–1568

    Article  PubMed  CAS  Google Scholar 

  • Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220:126–139

    Article  PubMed  CAS  Google Scholar 

  • Tani H, Torimura M, Akimitsu N (2013) The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells. PLoS ONE 8:e55684

    Article  PubMed  CAS  Google Scholar 

  • Washietl S, Hofacker IL, Lukasser M, Huttenhofer A, Stadler PF (2005) Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome. Nat Biotechnol 23:1383–1390

    Article  PubMed  CAS  Google Scholar 

  • Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504

    Article  PubMed  CAS  Google Scholar 

  • Woo CJ, Kingston RE (2007) HOTAIR lifts noncoding RNAs to new levels. Cell 129:1257–1259

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi H, Kojima T, Ito T, Kimura Y, Imamura M, Son S, Koizumi J, Murata M, Nagayama M, Nobuoka T, Tanaka S, Hirata K, Sawada N (2010) Transcriptional control of tight junction proteins via a protein kinase C signal pathway in human telomerase reverse transcriptase-transfected human pancreatic duct epithelial cells. Am J Pathol 177:698–712

    Article  PubMed  CAS  Google Scholar 

  • Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J, Fang G (2012) Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J 279:3159–3165

    Article  PubMed  CAS  Google Scholar 

  • Ying L, Huang Y, Chen H, Wang Y, Xia L, Chen Y, Liu Y, Qiu F (2013) Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst 9:407–411

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Gejman R, Mahta A, Zhong Y, Rice KA, Zhou Y, Cheunsuchon P, Louis DN, Klibanski A (2010) Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Res 70:2350–2358

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Zhang X, Klibanski A (2012) MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 48:R45–R53

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of General Surgery, RuiJin Hospital, Shanghai Jiaotong University School of Medicine, 197 RuiJin.Er.Road, ShangHai, 200025, China

    Xiongxiong Lu, Yuan Fang, Zhengting Wang, Junjie Xie, Qian Zhan, Xiaxing Deng, Hao Chen, Jiabin Jin, Chenghong Peng, Hongwei Li & Baiyong Shen

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  1. Xiongxiong Lu
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  2. Yuan Fang
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  3. Zhengting Wang
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  4. Junjie Xie
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  5. Qian Zhan
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  6. Xiaxing Deng
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  7. Hao Chen
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  8. Jiabin Jin
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  9. Chenghong Peng
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  10. Hongwei Li
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  11. Baiyong Shen
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Correspondence to Baiyong Shen.

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Xiongxiong Lu and Yuan Fang contributed equally to this work.

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Lu, X., Fang, Y., Wang, Z. et al. Downregulation of gas5 increases pancreatic cancer cell proliferation by regulating CDK6. Cell Tissue Res 354, 891–896 (2013). https://doi.org/10.1007/s00441-013-1711-x

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  • DOI: https://doi.org/10.1007/s00441-013-1711-x

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