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

Abstract

BackgroundGastric 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.MethodsExpression 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).ResultsWe 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.ConclusionOur 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.

Lentiviral-mediated overexpression of long non-coding RNA GAS5 reduces invasion by mediating MMP2 expression and activity in human melanoma cells

“…It is thought that low expression of GAS5 is associated with a higher possibility of lymph node metastasis and distant metastasis in non-small cell lung cancer and gastric cancer, although the differences are not significant (P=0.652 and P=0.056, respectively) (17,19). These findings further suggest that lncRNA GAS5 may function as a tumor suppressor and may represent a potential biomarker and new therapeutic target for some cancers.…”

“…GAS5 was originally isolated from NIH 3T3 cells by Schneider et al with the purpose of identifying potential tumor suppressor genes enriched during growth arrest induced by serum starvation (10). GAS5 transcript levels are significantly reduced in a spectrum of cancers including breast, prostate, glioblastoma, renal clear cell, bladder, hepatocellular, pancreatic, non-small cell lung, colorectal, cervical and multiple myeloma (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Importantly, aberrant GAS5 expression was significantly correlated with metastasis in cervical cancer (21) and hepatocellular carcinoma (15).…”

Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma

“…The lncRNA expression profiling data showed that there were lncRNAs that were differentially expressed between the PDAC tissues and matched adjacent non-tumor tissues. Previous studies showed that dysregulation of lncRNAs expression such as HOTAIR (32,33), HULC (34)(35)(36) and GAS5 (37,38), is a potential molecular marker for diagnostic and therapeutic purposes in several human cancers. There are still lncRNAs as potential novel candidate molecular markers for clinical diagnosis and therapy of PDAC that need to be further identified.…”

Long Noncoding RNA in Digestive Tract Cancers: Function, Mechanism, and Potential Biomarker

“…Sun et al stated that GAS5 was markedly downregulated in GC tissues, and its low expression correlated with the poor disease-free survival and overall survival of patients with GC. The ectopic expression of GAS5 repressed GC cell proliferation and induced apoptosis in vitro and in vivo through regulating E2F1 and P21 expression [67]. Franklin etal.…”