MicroRNA-936 induces cell cycle arrest and inhibits glioma cell proliferation by targeting CKS1.

Abstract

Accumulating evidence shows that microRNAs play important roles in cancers, including glioma. MiRNAs 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 miR-936 levels were downregulated in glioma specimens. Here, we further investigate the potential role of miR-936 in glioma. Quantitative reverse transcription-PCR was applied to detect the expression of mir-936 in glioma specimens. The direct targets of miR-936 were identified by bioinformatics analysis and were further validated by immunoblotting and luciferase reporter assay. The effects of miR-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 miR-936 on tumor growth and angiogenesis. Expression levels of miR-936 were greatly downregulated in glioma specimens, CKS1 was confirmed as a direct target of miR-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 miR-936. In vivo studies revealed that increased levels of miR-936 delayed the growth of tumors. Taken together, mir-936 may act as a glioma suppressor by targeting CKS1.