MicroRNA-379-5p Suppresses Tumours In Human Bladder Cancer By Directly Targeting MDM2

Aim of this studyBladder cancer is the second most common urological malignancy in the United States and is by far the most frequent urological malignancy in China.An increasing amount of evidence indicates that microRNAs perform extremely important functions in many biological processes relating to the formation and progression of cancers,including bladder cancer.Previous studies have reported that microRNA-379-5p(miR-379-5p)is involved in tumour initiation and development in human cancers.However,the expression pattern,biological functions and underlying mechanisms of miR-379-5p in bladder cancer remain unknown.MethodRT-qPCR were performed to detect miR-379-5p expression in bladder cancer tissues and cell lines.After transfection with miR-379-5p mimics or miR-NC in T24 and EJ cells,CCK8 and cell migration and invasion assays were used to investigate the effects of miR-379-5p on cell proliferation,migration and invasion.Subsequently,the direct target gene of miR-379-5p was explored using bioinformatics analysis,luciferase reporter assay,RT-qPCR and Western blot analysis.Furthermore,the roles of MDM2 in bladder cancer cells were examined.Moreover,rescue experiments were conducted to explore whether MDM2 is a direct target of miR-379-5p in bladder cancer.Besides,MDM2 expression in bladder cancer tissues were detected.Spearman' s correlation analysis were used to explore the association between miR-379-5p and MDM2 in bladder cancer tissues.ResultsThis study demonstrated that the expression levels of miR-379-5p in bladder cancer tissues and cell lines were lower than those in adjacent normal tissues and the human bladder epithelial immortalized SV-HUC-1 cell line.Restoration expression of miR-379-5p inhibited bladder cancer cell proliferation,migration and invasion.Mouse double minute 2(MDM2)was identified as a direct target gene of miR-379-5p.Furthermore,similar to miR-379-5p overexpression in bladder cancer cells,inhibition of MDM2 exerted tumour-suppressive effects.Rescue experiments showed that up-regulation of MDM2 reversed the inhibitory effects of miR-379-5p on bladder cancer cell proliferation,migration and invasion.MDM2 was highly expressed and inversely correlated with miR-379-5p expression in bladder cancer tissues.ConclusionsThese findings suggest that the miR-379-5p/MDM2 pathway plays an important role in bladder cancer and could serve as a potential candidate for bladder cancer therapeutics.