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ENAH在胃癌发生及预后中的意义。

The significance of ENAH in carcinogenesis and prognosis in gastric cancer.

作者信息

Wang Dan-Dan, Jin Qun, Wang Lei-Lei, Han Shu-Fang, Chen Yi-Bing, Sun Guo-Dong, Sun Shi-Fei, Sun Shu-Wang, Wang Tao, Liu Fan-Jie, Wang Ping, Shi Bin

机构信息

Shandong Medicinal Biotechnology Centre, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Back and Neck Pain Hospital of Shandong Academy of Medical Sciences, Jinan 250062, People's Republic of China.

The General Hospital of Jinan Military Command, Jinan 250012, People's Republic of China.

出版信息

Oncotarget. 2017 Aug 2;8(42):72466-72479. doi: 10.18632/oncotarget.19801. eCollection 2017 Sep 22.

DOI:10.18632/oncotarget.19801
PMID:29069803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5641146/
Abstract

The ENAH gene, which encodes a member of the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins, is involved in the assembly of actin filaments required for cell adhesion and motility. Recent studies show overexpressed ENAH in several cancer types, and ENAH correlates with tumor invasiveness. This study aimed to investigate the expression and function of ENAH in primary gastric adenocarcinoma, and its prognostic significance. We found significantly increased mRNA ( = 0.0283) and protein ( = 0.0301) expression of ENAH in gastric cancer tissues. ENAH expression markedly associated with tumor size ( < 0.001), T stage ( < 0.001), N stage ( = 0.001), TNM stage ( < 0.001) and prognosis ( < 0.001). Cox regression analyses revealed ENAH expression as an independent predictor of overall survival ( = 0.019). We also analyzed data of 155 gastric cancer cases from The Cancer Genome Atlas (TCGA) and found that ENAH expression significantly correlated with age ( = 0.003), T stage ( = 0.023) and prognosis ( = 0.05). Furthermore, the function of ENAH in cell proliferation, colony formation, cell migration and invasion of gastric cancer cells was analyzed . Knockdown of ENAH expression suppressed cell proliferation, colony formation, cell migration and invasion in MKN45 cells. Conversely, overexpression of ENAH promoted cell proliferation, cell migration and invasion in MGC803 cells. Our research suggests that ENAH might play promoting functions in carcinogenesis and progression of gastric cancer, and may serve as a valuable prognostic marker for primary gastric adenocarcinoma patients.

摘要

ENAH基因编码.enabled/血管舒张刺激磷蛋白(Ena/VASP)家族的一种蛋白质成员,参与细胞黏附和运动所需的肌动蛋白丝组装。最近的研究表明,ENAH在几种癌症类型中过表达,且ENAH与肿瘤侵袭性相关。本研究旨在探讨ENAH在原发性胃腺癌中的表达和功能及其预后意义。我们发现胃癌组织中ENAH的mRNA(P = 0.0283)和蛋白(P = 0.0301)表达显著增加。ENAH表达与肿瘤大小(P < 0.001)、T分期(P < 0.001)、N分期(P = 0.001)、TNM分期(P < 0.001)和预后(P < 0.001)显著相关。Cox回归分析显示ENAH表达是总生存的独立预测因子(P = 0.019)。我们还分析了来自癌症基因组图谱(TCGA)的155例胃癌病例的数据,发现ENAH表达与年龄(P = 0.003)、T分期(P = 0.023)和预后(P = 0.05)显著相关。此外,分析了ENAH在胃癌细胞增殖、集落形成、细胞迁移和侵袭中的功能。敲低ENAH表达可抑制MKN45细胞的增殖、集落形成、细胞迁移和侵袭。相反,ENAH过表达可促进MGC803细胞的增殖、细胞迁移和侵袭。我们的研究表明,ENAH可能在胃癌的发生和进展中发挥促进作用,并可能作为原发性胃腺癌患者有价值的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/ea5b2df5cca7/oncotarget-08-72466-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/46a2af25c262/oncotarget-08-72466-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/dfd8b326d0aa/oncotarget-08-72466-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/ea5b2df5cca7/oncotarget-08-72466-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/46a2af25c262/oncotarget-08-72466-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/dfd8b326d0aa/oncotarget-08-72466-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a68f/5641146/ea5b2df5cca7/oncotarget-08-72466-g004.jpg

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Evolution of Gastric Cancer Treatment: From the Golden Age of Surgery to an Era of Precision Medicine.
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Enabled homolog (ENAH) regulated by RNA binding protein splicing factor 3b subunit 4 (SF3B4) exacerbates the proliferation, invasion and migration of hepatocellular carcinoma cells via Notch signaling pathway.RNA 结合蛋白剪接因子 3b 亚基 4(SF3B4)调控的同源物(ENAH)通过 Notch 信号通路加剧肝癌细胞的增殖、侵袭和迁移。
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