Mechanism of miR-31-5p Promoting Proliferation,Migration and Invasion of Lung Adenocarcinoma by Targeting GFRA1
LIU Dasheng
DONG Lei
ZHANG Huiting
JIANG Jixun
AN Yujie
Abstract：Objective To analyze the mechanism of miR-31-5p promoting proliferation,migration and invasion of lung adenocarcinoma(LUAD)by targeting glial cell line-derived neurotrophic factorα1(GFRA1).Methods The expressions of miR-31-5p and GFRA1 in LUAD tissues and their relationship with clinical features were analyzed by bioinformatics.LUAD cells were divided into miR-NC group,miR-31-5p group,miR-31-5p+GFRA1 group,inhibitor NC group and miR-31-5p inhibitor group.The expression level of miR-31-5p in cells after transfection was detected by real-time fluorescence quantitative polymerase chain reaction.The cells'proliferation,migration and invasion capabilities were detected by functional experiments.Tumor weight and volume were detected by tumor formation assay in nude mice.The changes of GFRA1 level in different tissues were detected by immunohistochemistry.The expression level of GFRA1 protein was detected by Western Blot.The target gene of miR-31-5p was verified by dual luciferase reporter assay.Results The expression of miR-31-5p was up-regulated in LUAD and was related to malignant clinical phenotypes of LUAD(P<0.05).The relative expression level of miR-31-5p mRNA in the miR-31-5p group was higher than that in the miR-NC group,and the number of proliferating,migrating and invading cells was higher than that in the miR-NC group(P<0.05).The relative expression level of miR-31-5p mRNA in the miR-31-5p inhibitor group was lower than that in the inhibitor NC group,and the number of proliferating,migrating and invading cells was lower than that in the inhibitor NC group(P<0.05).The overexpression of miR-31-5p could promote the growth of xenograft tumors in nude mice and up-regulate GFRA1 levels(P<0.05).It was predicted by the Starbase database that GFRA1 was the target gene of miR-31-5p,which was verified by dual luciferase reporter assay.The relative expression levels of GFRA1 mRNA and protein in the miR-31-5p group were lower than those in the miR-NC group and the miR-31-5p+GFRA1 group(P<0.05).The expression of GFRA1 in LUAD tissue was lower than that in para-carcinoma tissues(P<0.05).The number of proliferating,migrating and invading cells in the miR-31-5p group was higher than that in the miR-NC group and the miR-31-5p+GFRA1 group(P<0.05).Conclusion The expression of miR-31-5p is up-regulated in LUAD,which can promote proliferation,migration and invasion of LUAD cells by up-regulating GFRA1.
Keywords：miR-31-5pGlial cell line-derived neurotrophic factorα1ProliferationMigrationInvasion
Publication Date：2025-01-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 196-203 )