PMID- 29908894 OWN - NLM STAT- MEDLINE DCOM- 20190726 LR - 20190726 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 142 DP - 2018 Sep TI - MicroRNA-499a decelerates glioma cell proliferation while accelerating apoptosis through the suppression of Notch1 and the MAPK signaling pathway. PG - 96-106 LID - S0361-9230(17)30697-4 [pii] LID - 10.1016/j.brainresbull.2018.06.005 [doi] AB - As the most common and lethal of intracranial tumors, glioma accounts for 81% of all malignant brain tumors. Research data have identified the role of microRNAs (miRs) as functional suppressors in the progression of Glioma. The present study aimed to, ascertain as to whether microRNA-499a (miR-499a) influences cell proliferation and apoptosis through the MAPK signaling pathway by targeting Notch1 in glioma. Both glioma and adjacent tissues between 2012-2016, were obtained from People's Hospital of Zhengzhou University (Henan Provincial People's Hospital). The collected glioma cells were treated with miR-449a mimic, miR-449a inhibitor, siRNA-Notch1, or SB230580 (an inhibitor of the MAPK signaling pathway). Verification of the targeting effect of miR-449a on Notch1 was provided by a dual-luciferase reporter gene assay. The expressions of miR-449a, Notch1, p38 mitogen-activated protein kinase (p38MAPK), extracellular regulated protein kinases (ERK1/2), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (bax), CyclinD1, and phosphorylation of p38MAPK (p-p38MAPK) and ERK1/2 (p-ERK1/2) in tissues and cells were detected by means of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis methods. Cellular processes of proliferation, cell cycle and apoptosis were evaluated by MTT and BrdU assays as well as flow cytometry, respectively. Notch1 was subsequently identified to be a target gene of miR-499a. After the cells were treated with miR-449a mimic, siRNA-Notch1 or SB230580, decreased expressions of Notch1, Bcl-2, CyclinD1, ERK1/2 and p-ERK1/2, cell proliferation as well as cells arrested at the S stage with elevated expressions levels of p38MAPK, p-p38MAPK, Bax, as well as increased cell apoptosis and number of cells arrested in G0/G1 stage were assessed. Taken together, based on the evidence obtained from the present study, assertions were subsequently made suggesting that MiR-499a targeted-inhibition of Notch1 may be a promising future therapeutic strategy for glioma treatment, by means of overexpressing of miR-499a resulting in the inhibition of glioma cell proliferation and promotion of cell apoptosis through suppression of the MAPK signaling pathway by decreasing Notch1. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Wang, Bang-Qing AU - Wang BQ AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China. FAU - Yang, Bin AU - Yang B AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China. FAU - Yang, Hua-Chao AU - Yang HC AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China; Henan University of Chinese Medicine, Zhengzhou 450046, PR China. FAU - Wang, Jun-Yi AU - Wang JY AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China; Henan University of Chinese Medicine, Zhengzhou 450046, PR China. FAU - Hu, Sen AU - Hu S AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China; Henan University of Chinese Medicine, Zhengzhou 450046, PR China. FAU - Gao, Yu-Shuai AU - Gao YS AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China. FAU - Bu, Xing-Yao AU - Bu XY AD - Department of Neurosurgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, PR China; Henan University of Chinese Medicine, Zhengzhou 450046, PR China. Electronic address: buxingyaozz@yeah.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180615 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (MIRN499 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NOTCH1 protein, human) RN - 0 (Receptor, Notch1) MH - Adolescent MH - Adult MH - Aged MH - Apoptosis/*physiology MH - Brain/metabolism/pathology/surgery MH - Brain Neoplasms/*metabolism/pathology/surgery MH - Cell Line, Tumor MH - Cell Proliferation/*physiology MH - Child MH - Female MH - Gene Expression Regulation, Neoplastic MH - Glioma/*metabolism/pathology/surgery MH - Humans MH - MAP Kinase Signaling System/physiology MH - Male MH - MicroRNAs/*metabolism MH - Middle Aged MH - Receptor, Notch1/metabolism MH - Young Adult OTO - NOTNLM OT - Apoptosis OT - Glioma OT - MAPK signaling pathway OT - MicroRNA-449a OT - Notch1 OT - Proliferation EDAT- 2018/06/18 06:00 MHDA- 2019/07/28 06:00 CRDT- 2018/06/18 06:00 PHST- 2017/11/22 00:00 [received] PHST- 2018/05/12 00:00 [revised] PHST- 2018/06/10 00:00 [accepted] PHST- 2018/06/18 06:00 [pubmed] PHST- 2019/07/28 06:00 [medline] PHST- 2018/06/18 06:00 [entrez] AID - S0361-9230(17)30697-4 [pii] AID - 10.1016/j.brainresbull.2018.06.005 [doi] PST - ppublish SO - Brain Res Bull. 2018 Sep;142:96-106. doi: 10.1016/j.brainresbull.2018.06.005. Epub 2018 Jun 15.