MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.
MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1.
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MeCP2 是 miR-638 的靶标，通过上调 GIT1 激活 MEK1/2-ERK1/2 信号通路，促进胃癌细胞增殖
DOI：
10.1038/oncsis.2017.60
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发表时间：
2017-07-31
期刊：
影响因子：
6.2
通讯作者：
Huang C
中科院分区：
文献类型：
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作者：
Zhao LY;Tong DD;Xue M;Ma HL;Liu SY;Yang J;Liu YX;Guo B;Ni L;Liu LY;Qin YN;Wang LM;Zhao XG;Huang C
甲基化CpG结合蛋白2（Methyl-CpG binding protein 2，MeCP 2）参与多种类型癌症的发生和进展。然而，其在胃癌（GC）中的确切作用及其相关分子机制仍不清楚。在本研究中，我们发现miR-638在胃癌组织和胃癌细胞系中的水平分别低于癌旁正常组织和正常胃上皮细胞系。低miR-638水平与肿瘤分化差、肿瘤大小和淋巴结转移相关。MeCP 2在胃癌组织中的表达水平高于癌旁正常组织。研究发现，miR-638可抑制胃癌细胞增殖、集落形成、G1-S期转换和肿瘤生长，并通过直接靶向MeCP 2诱导细胞凋亡。MeCP 2促进胃癌细胞增殖、集落形成和G1-S期细胞转换，抑制凋亡。分子机制的调查进行了使用集成的方法与微阵列分析，染色质免疫沉淀测序和报告基因测定的组合。结果表明，MeCP 2与G蛋白偶联受体激酶相互作用蛋白1（GIT 1）启动子甲基化CpG岛结合，上调其表达，从而激活MEK 1/2-ERK 1/2信号通路，促进GC细胞增殖。综上所述，我们的研究表明，MeCP 2，miR-638的靶点，通过上调GIT 1激活MEK 1/2-ERK 1/2信号通路，促进GC细胞增殖并诱导细胞周期进程。这些发现表明MeCP 2在GC进展中起着重要作用，并可能作为GC治疗的潜在靶点。
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.
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影响因子：
--
作者：
Bhattacharya A;Schmitz U;Raatz Y;Schönherr M;Kottek T;Schauer M;Franz S;Saalbach A;Anderegg U;Wolkenhauer O;Schadendorf D;Simon JC;Magin T;Vera J;Kunz M
通讯作者：
Kunz M
DOI：
10.1126/science.1183621
发表时间：
2010-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kasowski M;Grubert F;Heffelfinger C;Hariharan M;Asabere A;Waszak SM;Habegger L;Rozowsky J;Shi M;Urban AE;Hong MY;Karczewski KJ;Huber W;Weissman SM;Gerstein MB;Korbel JO;Snyder M
通讯作者：
Snyder M
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
4.3
作者：
Lujambio, Amaia;Esteller, Manel
通讯作者：
Esteller, Manel
影响因子：
64.5
作者：
Baker SA;Chen L;Wilkins AD;Yu P;Lichtarge O;Zoghbi HY
通讯作者：
Zoghbi HY