Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer.

INTRODUCTION Cervical cancer is the second leading cause of cancer morbidity and mortality for women around the world. Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although downregulation of lncRNA GAS5 in several cancers has been studied, its role in cervical cancer remains unknown. The aim of this study is to investigate the expression, clinical significance and biological role in cervical cancer. METHODS Expression of GAS5 was analyzed in cervical cancer tissues by quantitative Real-time PCR (qRT-PCR). And its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress GAS5 expression in cervical cancer cells. In vitro assays were performed to further explore the biological functions of GAS5 in cervical cancer. RESULTS We found that GAS5 expression was markedly downregulated in cervical cancer tissues than in corresponding adjacent normal tissues. Decreased GAS5 expression was significantly correlated with FIGO stage, vascular invasion and lymph node metastasis. Moreover, cervical cancer patients with GAS5 lower expression have shown significantly poorer overall survival than those with higher GAS5 expression. And GAS5 expression was an independent prognostic marker of overall survival in a multivariate analysis. In vitro assays our data indicated that knockdown of GAS5 promoted cell proliferation, migration, and invasion. CONCLUSIONS Our study presents that lncRNA GAS5 is a novel molecule involved in cervical cancer progression, which provide a potential prognostic biomarker and therapeutic target.

[1]  J. Mattick,et al.  Non-coding RNA. , 2006, Human molecular genetics.

[2]  A. Jemal,et al.  Cancer statistics, 2013 , 2013, CA: a cancer journal for clinicians.

[3]  Xing-Hua Li,et al.  Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. , 2014, International journal of clinical and experimental pathology.

[4]  R. Qin,et al.  Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. , 2013, Neoplasma.

[5]  Lennart Philipson,et al.  Genes specifically expressed at growth arrest of mammalian cells , 1988, Cell.

[6]  Jiajia Wang,et al.  Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. , 2010, Acta biochimica et biophysica Sinica.

[7]  Naoki Takahashi,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. , 2008, Cancer genetics and cytogenetics.

[8]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[9]  Jun-Tao Jiang,et al.  Downregulation of GAS5 Promotes Bladder Cancer Cell Proliferation, Partly by Regulating CDK6 , 2013, PloS one.

[10]  Ming Sun,et al.  Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer , 2014, BMC Cancer.

[11]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[12]  R. Qin,et al.  Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. , 2013, Neoplasma.

[13]  E. Lander Initial impact of the sequencing of the human genome , 2011, Nature.

[14]  S. Waggoner Cervical cancer , 2003, The Lancet.

[15]  A. Chinnaiyan,et al.  The emergence of lncRNAs in cancer biology. , 2011, Cancer discovery.

[16]  Howard Y. Chang,et al.  Long noncoding RNAs and human disease. , 2011, Trends in cell biology.

[17]  S. Wacholder,et al.  Human papillomavirus testing in the prevention of cervical cancer. , 2011, Journal of the National Cancer Institute.

[18]  L. Stalpers,et al.  Prognostic model for survival in patients with early stage cervical cancer , 2011, Cancer.

[19]  Carolyn J. Brown,et al.  The functional role of long non-coding RNA in human carcinomas , 2011, Molecular Cancer.

[20]  M. Mourtada-Maarabouni,et al.  GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer , 2009, Oncogene.

[21]  M. Zheng,et al.  Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer , 2014, Archives of Gynecology and Obstetrics.