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MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.

ABSTRACT: Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain unknown. In the present study, we found that miR-638 levels were lower in GC tissues and GC cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, respectively. Low miR-638 levels were associated with poor tumor differentiation, tumor size and lymph node metastasis. MeCP2 expression levels were higher in GC tissues than in adjacent normal tissues. It was found that miR-638 inhibited GC cell proliferation, colony formation, G1-S transition and tumor growth, and induced cell apoptosis by directly targeting MeCP2. MeCP2 promoted GC cell proliferation, colony formation and G1-S cell-cycle transition, and suppressed apoptosis. Molecular mechanistic investigations were performed using an integrated approach with a combination of microarray analysis, chromatin immunoprecipitation sequencing and a reporter gene assay. The results showed that MeCP2 bound to the methylated CpG islands of G-protein-coupled receptor kinase-interacting protein 1 (GIT1) promoter and upregulated its expression, thereby activating the MEK1/2-ERK1/2 signaling pathway and promoting GC cell proliferation. Taken together, our study demonstrates that MeCP2, a target of miR-638, facilitates GC cell proliferation and induces cell-cycle progression through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1. The findings suggest that MeCP2 plays a significant role in GC progression, and may serve as a potential target for GC therapy.

SUBMITTER: Zhao LY

PROVIDER: S-EPMC5541712 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.

Zhao L Y LY Tong D D DD Xue M M Ma H L HL Liu S Y SY Yang J J Liu Y X YX Guo B B Ni L L Liu L Y LY Qin Y N YN Wang L M LM Zhao X G XG Huang C C

Oncogenesis 20170731 7

Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain unknown. In the present study, we found that miR-638 levels were lower in GC tissues and GC cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, respectively. Low miR-638 levels were associated with poor tumor differentiation, tumor size and lymph node metast ...[more]

PMID: 28759023

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Project description:Long non?coding RNAs (lncRNAs) have been validated to mediate the development of atherosclerosis (AS). In the present study, the molecular mechanisms and functions of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in the advancement of human aortic endothelial cells (HAECs) were investigated. The levels of lncRNA?NEAT1 and miR?638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK?8 assays were performed to determine the proliferative capacity of cells, and the apoptotic capacity of cells was analyzed on the basis of apoptotic cell proportion and caspase?3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR?638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki?67, proliferating cell nuclear antigen, PGK1, Bax, Bcl?2, (p)?mTOR, (p)?AKT, and ??catenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized low?density lipoprotein (ox?LDL), the expression level of miR?638 was decreased, whereas that of NEAT1 was increased. After ox?LDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR?638 inhibitor. NEAT1 inhibited miR?638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR?638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR?638. Additionally, the miR?638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in ox?LDL?induced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR?638 in ox?LDL?induced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.

Dataset Information

MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.

Publications

MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.

Similar Datasets

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