MicroRNA-936 Induces Cell Cycle Arrest And Inhibits Glioma Cell Proliferation By Targeting CKS1

Background: Accumulating evidence shows that micro RNAs play important roles in cancers,including glioma.Mi RNAs have been shown to participate in a variety of cellular functions including cell apoptosis,cell proliferation,neural development,and stem cell differentiation.Previous studies reported that mi R-936 levels were downregulated in glioma specimens.Here,we further investigate the potential role of mi R-936 in glioma.Methods: Quantitative reverse transcription-PCR was applied to detect the expression of mi R-936 in glioma specimens.The direct targets of mi R-936 were identified by bioinformatics analysis and were further validated by immunoblotting and luciferase report assay.The effects of mi R-936 on glioma cell proliferation and cell cycle of glioma cells were analyzed by Cell-Counting Kit 8 assay,colony formation,5-ethynyl-2-deoxyuridine(EDU)and flow cytometry assays.A xenograft model was used to study the effect of mi R-936 on tumor growth and angiogenesis.Result: Expression levels of mi R-936 were greatly downregulated in glioma specimens,CKS1 was confirmed as a direct target of mi R-936.The glioma cell cycle was blocked to G1 by negatively regulating CKS1 and its downstream signaling pathway,Akt-ERK1/2.Furthermore,overexpression of CKS1 rescued the inhibitory effects of mi R-936.In vivo studies revealed that increased levels of mi R-936 delayed the growth of tumors.Conclusion: Taken together,mi R-936 may act as a glioma suppressor by targeting CKS1.