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LncRNA MALAT1 Regulates The PI3K/Akt Signaling Pathway By Targeting MiR-146a To Affect The Proliferation,Migration And Invasion Of Gastric Cancer Cells

Posted on:2024-04-30Degree:MasterType:Thesis
Country:ChinaCandidate:Y N GaoFull Text:PDF
GTID:2544307127975119Subject:Internal Medicine
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Objective: Long non-coding RNA lung adenocarcinoma metastasis-associated transcript 1can bind to a variety of micro RNAs to form a tumor regulatory network and plays a key role in tumorigenesis and invasion.However,the relevance and mechanism of action of MALAT1 and mi R-146 a in gastric cancer are not clear.To explore the effects and mechanism of lnc RNA MALAT1 on the proliferation,migration and invasion of gastric cancer cells by regulating mi R-146 a and the aim is to provide new directions for the diagnosis and treatment of gastric cancer.Methods: GC tissue and matched normal gastric epithelial tissue were collected,GC cells MKN-45 were separated into blank control(BC)group(untransfected),MALAT1 si RNA-NC group(transfected with MALAT1 si RNA-NC),MALAT1 si RNA group(transfected with MALAT1 si RNA),mi R-146 a mimics-NC group(transfected with mi R-146 a mimics-NC),mi R-146 a mimics group(transfected with mi R-146 a mimics),MALAT1 si RNA+mi R-146 a inhibitor-NC group(co-transfected with MALAT1 si RNA+mi R-146 a inhibitor-NC)and MALAT1 si RNA+mi R-146 a inhibitor group(co-transfected with MALAT1 si RNA+mi R-146 a inhibitor).Quantitative fluorescent PCR(q RT-PCR)was performed to measure the expression of MALAT1 and mi R-146 a in gastric tissue or cells;clone formation experiment and CCK-8 experiment were performed to measure proliferation ability;Transwell method was performed to measure invasion and migration abilities;RNA pull down experiment and dual luciferase report experiment were performed to analyze the binding of MALAT1 and mi R-146a;Western blot was performed to measure the expression of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)pathway protein,c-Myc and matrix metalloproteinase 9(MMP9)protein.Results: Transfection of MALAT1 si RNA was able to obviously reduce the expression of MALAT1 in MKN-45 cells.Knockdown of MALAT1 or overexpression of mi R-146 a was able to reduce cell viability,cloning ability,migration and invasion,increase mi R-146 a expression,and reduce PI3Kp85α,PI3Kp85β,c-Myc,MMP9 protein expression and p-Akt/Akt level;MALAT1 was able to bind to and target down-regulation of mi R-146 a expression;low expression of mi R-146 a was able to reverse the inhibitory effects of knocking down MALAT1 on the proliferation,migration and invasion of MKN-45 cells.Conclusion: MALAT1 may be used as ce RNA to adsorb and degrade mi R-146 a.Knockdown of MALAT1 can up-regulate the expression of mi R-146 a,and inhibit the proliferation,migration and invasion of GC cells through the PI3K/Akt pathway.
Keywords/Search Tags:LncRNA, MALAT1, microRNA-146a, PI3K/Akt pathway, gastric cancer
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