MicroRNA-let-7a Regulates Cell Autophagy By Targeting Rictor In Gastric Cancer Cell

Background:Gastric cancer is one of the leading causes of cancer-related death worldwide.The vast majority of cases occur in East Asia,and the mortality rate is high.In China,gastric cancer is the third most common malignancy.Autophagy is an evolutionary process that involves the degradation of organelles and cytoplasmic components within the lysosome,which is extremely important for maintaining homeostasis in cells.MicroRNAs could combine the 3 '-non translation region(3'-UTR)of the target gene to inhibit the translation or accelerate its degradation,so as to regulate the expression of target gene at post transcriptional level or translation level.It is reported that miRNA participates in the regulation of autophagy in many diseases.Our previous studies have shown that mi R-let-7a can play an anti-tumor role as an anti-tumor gene and inhibit the proliferation,migration and invasion of gastric cancer cells.However,the effect of miR-let-7a on autophagy in gastric cancer cells is unclear.Objective:To investigate the effect of miR-let-7a on autophagy in gastric cancer cells and related molecular mechanisms,and to to study the role of the Rictor/Akt-mTOR signaling pathway in miR-let-7a-induced autophagy in gastric cancer cells in order to provide new strategies for discovering new serum biomarkers,improving early diagnosis of gastric cancer,and improving the treatment of gastric cancer patients.Methods:1.Construction of miR-let-7a interference/overexpression stably transfected gastric cancer cell lines.2.The effect of miR-let-7a on autophagy in gastric cancer cells was detected by immunofluorescence and Western blot.3.Bioinformatics analysis and dual luciferase reporter assays verify that miR-let-7a directly binds to the autophagy-related target gene Rictor.4.The recovery experiment further verified whether miR-let-7a binds directly to the target gene Rictor.5.Explore whether miR-let-7a affects autophagy through the Rictor/Akt-mTOR pathway.Results:1.Immunofluorescence experiments and Western blot experiments showed that miR-let-7a can promote autophagy in gastric cancer cells.2.Bioinformatics analysis and dual luciferase reporter assays showed that miRlet-7a binds directly to the autophagy-related target gene Rictor.3.Further verification of mRNA and protein levels showed that miR-let-7a binds directly to Rictor.4.Protein recovery experiments and immunofluorescence recovery experiments showed that miR-let-7a promotes autophagy in gastric cancer cells through the Rictor/Akt-mTOR pathway.Conclusion:MicroRNA-let-7a promotes autophagy in gastric cancer cells through targeted regulation of the Rictor/Akt-mTOR pathway and may serve as a potential therapeutic target for the comprehensive treatment of gastric cancer.