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07 December 2014 : Laboratory Research

MiR-210 Up-Regulation Inhibits Proliferation and Induces Apoptosis in Glioma Cells by Targeting SIN3A

Chao ShangAEG, Yang HongB, Yan GuoC, Yun-hui LiuCD, Yi-xue XueAE

DOI: 10.12659/MSM.892994

Med Sci Monit 2014; 20:2571-2577

Abstract

BACKGROUND: The aim of this study was to determine whether miR-210 can affect the apoptosis and proliferation of human U251 glioma cells from down-regulating SIN3A.

MATERIAL AND METHODS: The expression of miRNA-210 was detected by quantitative real-time PCR in normal brain tissue and glioma samples. The apoptosis and proliferation ability of U251 cells were analyzed by MTT and flow cytometry assay after anti-miR-210 transfection. For the regulation mechanism analysis of miR-210, TargetScan, PicTar, and microRNA were selected to predict some potential target genes of miR-210. The predicted gene was identified to be the direct and specific target gene of miR-210 by luciferase activities assay and Western blot. RNA interference technology was used to confirm that the apoptosis and proliferation effects of miR-210 were directly induced by SIN3A.

RESULTS: The expression of miR-210 increased significantly in glioma in comparison with normal brain tissue. The silence of miR-210 expression could inhibit the proliferation of U251 cells and induce the apoptosis. Mechanism analysis revealed that SIN3A was a specific and direct target gene of miR-210. The siRNA-SIN3A could down-regulate the expression of SIN3A protein, which was up-regulated in U251 cells by anti-miR-210 transfection, and our experiments found that silence of SIN3A could inhibit the apoptosis and sharply increase the proliferation of U251 cells. The regulation effects of anti-miR-210 on apoptosis and proliferation can be reversed respectively by the expression silence of SIN3A.

CONCLUSIONS: Aberrantly expressed miR-210 regulates human U251 glioma cells apoptosis and proliferation partly through directly down-regulating SIN3A protein expression. This might offer a new potential therapeutic stratagem for glioma.

Keywords: 3' Untranslated Regions - genetics, Apoptosis - genetics, Base Sequence, Brain Neoplasms - pathology, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Glioma - pathology, MicroRNAs - metabolism, Molecular Sequence Data, Real-Time Polymerase Chain Reaction, Repressor Proteins - metabolism, Up-Regulation - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750