IncRNA Meg3 Induces Apoptosis In Gastric Cancer Cells Via Regulating MiR-17-5p/PTEN/Akt Signaling Pathway

Gastric cancer is the second most popular malignant tumor in the world,and there are more than one million new cases every year.Meanwhile,China is a country with high incidence of gastric cancer,accounting for almost half of the cases in the whole world.The early symptoms of gastric cancer are not typical,easy to invade and metastasize,and the prognosis is poor.The five-year survival rate is less than 10%Therefore,exploring the molecular mechanism of the development and progression of gastric cancer is of great significance for the diagnosis and treatment of gastric cancerA large number of studies in recent years have proved that long non-coding RNA(lncRNA)plays an important role in various biological processes such as transcription,translation and epigenetic regulation.Maternally expressed gene 3(Meg3)is a tumor suppressor gene,and its transcription product lncRNA Meg3 is associated with the development of cancer.Studies have shown that it is significantly reduced in many tumors,but currently there are only a few of studies focusing on its biological effects and molecular mechanisms in gastric cancer.MicroRNA(miRNA)is also closely related to cancer development.In recent years,studies have shown that lncRNAs can affect the progression of cancer by altering the function of miRNA.This study aimed to elucidate the expression of lncRNA Meg3 in gastric cancer and the mechanism of the apoptosis of gastric cancer cells induced by its interaction with miR-17-5p,and further provide a new target for the treatment of gastric cancerObjective:To investigate the molecular mechanism of the apoptosis of gastric cancer cells induced by long-chain non-coding RNA Meg3 through PTEN/PI3K/Akt signaling pathwayMethods:The levels of Meg3,miR-17-5p and PTEN in gastric cancer specimens were determined by RT-qPCR and Western blot,which were compared with adjacent non-cancerous normal tissues.After using the algorithm to predict the target gene of miR-17-5p,the effect of Meg3 on the miR-17-5p/PTEN pathway was verified by luciferase reporter assay,and Meg3 and miR-17-5p were colocalized using in situ hybridization.Finally,Meg3 overexpression or inhibition was performed on SGC-7901 gastric cancer cell line and the changes of PI3K/Akt pathway and apoptosis were detectedResults:Compared with adjacent non-cancerous tissues,the levels of Meg3 and PTEN protein in gastric cancer tissues were significantly down-regulated,the difference was statistically significant(p<0.05),while the levels of miR-17-5p and PTEN mRNA were not significantly changed.Bioinformatic prediction results and intracellular fluorescence colocalization experiments showed that miR-17-5p binded to the 3’-untranslated region of PTEN and also had the ability to bind Meg3.The luciferase reporter gene assay showed that Meg3 overexpression inhibited the binding of miR-17-5p to the 3’-untranslated region of PTEN,thereby increasing PTEN protein expression and blocking the PI3K/Akt pathway to promote apoptosis of gastric cancer cellsConclusions:Long-chain non-coding RNA Meg3 reduces the inhibition of PTEN expression by competitive binding to miR-17-5p,thereby inhibiting PI3K/Akt signaling pathway and promoting apoptosis of gastric cancer cells.