The Study Of LncRNA MIR4435-2HG In Gastric Cancer Carcinogenesis

Gastric cancer(GC)is the fourth most common malignant tumors in China.The therapeutic effect is far from ideal,and the five-year survival rate is only up to 30%because of its aggressive behavior and the fact that it is diagnosed at progressive stage.Therefore,it’s urgent to carry out the basic research of GC and exploring its molecular mechanism to provide more efficient strategies for the diagnosis and treatment.Recently,a various of studies shown that long non coding RNAs(LncRNAs)play a very important role in the occurrence and development of tumors by promoting cell proliferation,eliminating growth inhibition,and inhibiting apoptosis.Many evidences indicate that LncRNAs contribute to the occurrence and development of GC.Dozens of lncRNAs have been reported to play an important role in GC cell proliferation,apoptosis migration and invasion.The study of GC related IncRNA has shown good prospects in the the pathogenesis of GC and new biomarkers.In previous work,we found that LncRNA MIR4435-2HG is highly expressed in gastric cancer by LncRNA microarray and bioinformatics analysis.It is probably one of the important LncRNA regulating gastric cancer phenotype.Purpose:To study the function and molecular mechanism of IncRNA MIR4435-2HG on gastric cancer(GC).Methods:First,the expression of MIR4435-2HG in GC tissues was compared with that in normal tissues.Second,typical GC cells were selected as the model cells and they were stably transfected with specific shRNA towards MIR4435-2HG;then nude mice were selected as the model animal and they were inoculated with specifically modified GC cells.Third,the effects of MIR4435-2HG on the specific GC cells,specific molecules and specific nude mice were studied.Results:First,the expression of MIR4435-2HG was found to be higher than that in normal tissues.Second,at the cellular level,the knockdown of MIR4435-2HG was found able to inhibit the proliferation,migration,invasion,tumorigenesis and cancerous progression of GC cells,and to promote the apoptosis and cell cycle G1 arrest of GC cells.Third,at animal level,the knockdown of MIR4435-2HG was found able to decrease the weight and volume of tumor tissue.Fourth,at the molecular level,MIR4435-2HG was found able to influence the expression levels of proteins important in epithelial-mesenchymal transition(EMT),bind the protein Desmoplakin(DSP),reduce the expression of DSP gene,influence the Wnt/β-catenin pathway through DSP and influence the expression levels of proteins important in EMT.Conclusions:MIR4435-2HG held comprehensive effects on the tumorigenesis and progression of GC at tissue level,cellular level and molecular level.Specifically,knockdown of MIR4435-2HG could inhibit the tumorigenesis and progression of GC,and MIR4435-2HG could affect EMT through DSP,which finally influence the tumorigenesis and progression of GC.