The Expression And Function Of MALAT2 In Gastric Cancer

OBJECTIVEThe purpose of this study is to investigate the role of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 2(MALAT2)in the prognosis of stage ?/? gastric cancer(GC)patients.RESEARCH DESIGN AND METHODSThe expression of MALAT2 was evaluated in cancer tissues from 146 stage ?/? GC patients undergoing radical resection and paired normal samples using quantitative real-time reverse transcriptase RT-PCR.Differences in the expression of MALAT2 between 146 GC and paired normal gastric mucosa samples were analyzed with the Chi-square test.The relationships among the MALAT2 expression,disease-free survival(DFS)and overall survival(OS)were analyzed using the univariate KaplanMeier method and the multivariate COX regression model.Through transwell migration assay and wound healing experiment,we could determine the migration and invasion ability of gastric carcinoma cells with different MALAT2 expression levels which was infected by recombinant lenti-viruses.By using gastric carcinoma cells with stable MALAT2 expression that was treated with different types of lenti-viruses,we detected the expression of MALAT2 and the levels of E-cadherin and vimentin as the EMT markers with RT-PCR and Western blot technique,and investigated the correlations between them.Finally,we treated the MALAT2 upregulated gastric carcinoma cells with the MEK inhibitor,U0126.The invasion ability of gastric carcinoma cells were assessed by transwell migration assay.We determine the expression levels of E-cadherin and vimentin with real-time RT-PCR and Western blot.RESULTSThe quantitative polymerase chain reaction results showed that MALAT2 was frequently over-expressed in cancer tissues and this over-expression was found to significantly correlate with perineural invasion and TNM staging.The ectopic expression of MALAT2 contributed to the migration of human GC SGC-7901 cells,whereas knockdown of MALAT2 inhibited the migration of the SGC-7901 cells in vitro.Further investigation into the underlying mechanisms responsible for the migratory effects revealed that MALAT2 induced the epithelial-mesenchymal transition(EMT)through an MEK/extracellular signal-regulated kinase-dependent mechanism as treatment with the MEK inhibitor,U0126,decreased migration and reversed the EMT in the MALAT2 over-expressed SGC-7901 cells.CONCLUSIONSThe expression of MALAT2 is upregulated in GC tissues,and a higher expression level of MALAT2 might serve as a negative prognostic marker in stage ?/? GC patients which implies the potential application of MALAT2 in the therapeutic treatment of GC.