Study On Let-7a-3p Regulating Invasion And Migration Ability Of A549 Cells By Targeting CXCR4

Objective: The CXCL12/CXCR4 signaling aix plays an important role in the metastasis of malignant tumors.Let-7a-3p expression is down-regulated in lung cancer tissues,and reporter gene analysis results indicated that CXCR4 might be its potential target gene.This study aims to validate that let-7a-3p can down-regulate CXCR4 expression in A549 cells,and inhibit the invasion and migration ability of A549 cells.Methods:(1)The mRNA expression of let-7a-3p and CXCR4 in A549 cells are detected by qRT-PCR.(2)The expression of CXCR4 mRNA and protein are analyzed by qRT-PCR and Western Blot after let-7a-3p mimic or inhibitor are transfected into A549 cells.(3)Luciferase reporter gene assay is uesd to verify let-7a-3p binding to CXCR4 3,-UTR.(4)Transwell assay is applied to analyze the effects of CXCR4 expression on cell invasion and metastasis after CXCR4 overexpressed or silenced;associated MMPs expression are analyzed by qRT-PCR and Western Blot.(5)After let-7a-3p mimic or inhibitor are transfected into A549 cells,MMPs expression are detectd,as well as their effects on invasion and migration ability of A549 cells.Results:(1)Let-7a-3p expression is down-regulated,and CXCR4 is up-regulated in A549 cells.(2)Let-7a-3p can negatively regulate the expression of CXCR4.(3)The Luciferase reporter gene plasmid containing CXCR4 3,-UTR was constructed successfully,which can be used to confirm the targeted binding of let-7a-3p with CXCR4.(4)Overexpression of CXCR4 promotes the invasion and migration of A549 cells,and up-regulated the expression of MMP-2、MMP-9.However,low expression of CXCR4 has the opposite effects.(5)Let-7a-3p can negatively regulate the expression of CXCR4 and down-regulate the expression levels of MMP-2 and MMP-9 to inhibit the invasion and migration ability of A549 cells.Conclusion: Let-7a-3p inhibits the invasion and migration ability of A549 cells by targeting CXCR4 as well as down-regulating the expression of MMP-2、MMP-9.