Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer

BMC Cancer

Ming Sun³  Fei-yan Jin³  Rui Xia³  Rong Kong³  Jin-hai Li¹  Tong-peng Xu²  Yan-wen Liu³  Er-bao Zhang³  Xiang-hua Liu³  Wei De³ 

[1] Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

[2] Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

[3] Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, People’s Republic of China

关键词: Cell proliferation;    Poor prognosis;    GAS5;    Long noncoding RNA;    Gastric cancer;   

Others  :  858839
DOI  :  10.1186/1471-2407-14-319

 received in 2013-12-13, accepted in 2014-05-02,  发布年份 2014

【 摘 要 】

Background

Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer.

Methods

Expression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 -GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed).

Results

We found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218–0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression.

Conclusion

Our study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.

【 授权许可】

   
2014 Sun et al.; licensee BioMed Central Ltd.

【 图 表 】

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