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受MiR-30c-2-3p靶向的RAB31调控GLI1信号通路,影响胃癌细胞增殖和凋亡。

RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis.

作者信息

Tang Chao-Tao, Liang Qian, Yang Li, Lin Xiao-Lu, Wu Shan, Chen Yong, Zhang Xin-Tian, Gao Yun-Jie, Ge Zhi-Zheng

机构信息

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.

出版信息

Front Oncol. 2018 Nov 26;8:554. doi: 10.3389/fonc.2018.00554. eCollection 2018.

Abstract

Gastric cancer (GC), one of the most common cancers worldwide, is highly malignant and fatal. Ras-related protein in brain 31 (RAB31), a member of the RAB family of oncogenes, participates in the process of carcinogenesis and cancer development; however, its role in GC progression is unknown. In our study, 90 pairs of tissue microarrays were used to measure the levels of RAB31 protein by immunochemistry, and 22 pairs of fresh tissue were used to measure the levels of RAB31 mRNA by quantitative PCR. We also investigated the effects of RAB31 on tumor growth both and . RAB31 was overexpressed in GC tissues, and its overexpression predicted poor survival in patients. In a nude mouse model, depletion of RAB31 inhibited tumor growth. , silencing of RAB31 suppressed cell viability, promoted cell cycle arrest, enhanced apoptosis, and affected the expression of cell cycle and apoptotic proteins; these effects were mediated by glioma-associated oncogene homolog 1 (GLI1). Co-immunoprecipitation and immunofluorescence assays confirmed that RAB31 interacted with GLI1. In addition, luciferase reporter assays and Western blotting showed that microRNA-30c-2-3p modulated the RAB31/GLI1 pathway by targeting the 3'-untranslated region of RAB31. Collectively, these data show that RAB31 is regulated by microRNA-30c-2-3p, and functions as an oncogene in GC tumorigenesis and development by interacting with GLI1. Therefore, targeting the miR-30c-2-3p/RAB31/GLI1 axis may be a therapeutic intervention for gastric cancer.

摘要

胃癌(GC)是全球最常见的癌症之一,具有高度恶性和致命性。脑 Ras 相关蛋白 31(RAB31)是 RAB 癌基因家族的成员之一,参与致癌和癌症发展过程;然而,其在 GC 进展中的作用尚不清楚。在我们的研究中,使用 90 对组织芯片通过免疫化学方法检测 RAB31 蛋白水平,使用 22 对新鲜组织通过定量 PCR 检测 RAB31 mRNA 水平。我们还研究了 RAB31 对肿瘤生长的体内和体外影响。RAB31 在 GC 组织中过表达,其过表达预示患者生存不良。在裸鼠模型中,RAB31 的缺失抑制肿瘤生长。此外,RAB31 的沉默抑制细胞活力,促进细胞周期停滞,增强细胞凋亡,并影响细胞周期和凋亡蛋白的表达;这些作用由胶质瘤相关癌基因同源物 1(GLI1)介导。免疫共沉淀和免疫荧光分析证实 RAB31 与 GLI1 相互作用。此外,荧光素酶报告基因检测和蛋白质印迹表明,微小 RNA-30c-2-3p 通过靶向 RAB31 的 3'非翻译区调节 RAB31/GLI1 通路。总体而言,这些数据表明 RAB31 受微小 RNA-30c-2-3p 调控,并通过与 GLI1 相互作用在 GC 肿瘤发生和发展中发挥癌基因作用。因此,靶向 miR-30c-2-3p/RAB31/GLI1 轴可能是胃癌的一种治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fd1/6275292/4c05e399995c/fonc-08-00554-g0001.jpg

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