MiR-138-5p Inhibits The Growth And Invasion Of Glioma Cells By Regulating WEE1

Purpose:miRNAs play an important role in many human tumors,and more and more evidences indicate that miRNAs also play an important regulatory role in the occurrence and development of gliomas.In the previous bioinformatics studies,our group found that the expression of miR-138-5p was decreased in gliomas,and miR-138-5p may play a tumor suppressive role in gliomas.However,the regulation and mechanism of miR-138-5p in the malignant biological behavior of glioma have not been clarified.Many studies have shown that WEE1 is one of the important regulatory targets of miR-138-5p in tumors.In this study,our group investigated whether miR-138-5p affects the malignant biological characteristics of gliomas by regulating the expression of WEE1.Methods:In this study,the RNA levels of miR-138-5p and WEE1 in glioma cells(U87 and U251)treated by different methods were detected by QRT-PCR.The expression levels of WEE1,Vimentin and N-cadherin in glioma cells treated by different methods were detected by Western Blotting.Transwell assay was used to detect the effects of transfection of miR-138-5P and/or WEE1 on the metastasis and invasion of glioma cells.The activity of glioma cells transfected with miR-138-5P and/or WEE1 was determined by CCK-8 assay.The effects of transfection of miR-138-5P and/or WEE1 on the proliferation of glioma cells were detected by clonogenesis assay.The apoptosis rate of glioma cells transfected with miR-138-5p and/or WEE1 was determined by flow cytometry.The regulatory relationship between miR-138-5p and WEE1 was detected by dual luciferase.Results:Functional studies showed that overexpression of miR-138-5p in glioma cell lines(U87 and U251)inhibited proliferation,invasion and cell activity,and decreased expression of invasion-related proteins Vimentin and N-cadherin,and apoptosis rate of glioma cells significantly increased after transfection with miR-138-5p.Although the dual luciferase assay failed to prove that WEE1 was a direct regulatory target of miR-138-5p,overexpression of miR-138-5p significantly inhibited the m RNA and protein levels of WEE1 in glioma cells.In addition,the reintroduction of WEE1 partially eliminated the inhibition of mir-138-5p on the proliferation,invasion and cell activity of glioma cells,the expression of invasion-related proteins Vimentin and N-cadherin increased,and the apoptosis rate of glioma cells decreased significantly after WEE1 reintroduction.Therefore,our research group could identify WEE1 as the target of miR-138-5p.Conclusions:The study of our group showed that miR-138-5p was low expressed in glioma,and miR-138-5p had tumor inhibition effect on glioma.miR-138-5p can inhibit the proliferation,invasion and cell activity of glioma by regulating WEE1,and also increase the apoptosis of glioma.These data provide new insights into the molecular mechanisms underlying glioma genesis and development.Figures: 12,tables: 9,references: 77...