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RUNX3通过靶向miR-186/E-钙黏蛋白/上皮-间质转化途径调控肝癌细胞转移。

RUNX3 regulates hepatocellular carcinoma cell metastasis via targeting miR-186/E-cadherin/EMT pathway.

作者信息

Gou Yuli, Zhai Fangbing, Zhang Liang, Cui Lan

机构信息

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning, China.

Department of Radiology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning, China.

出版信息

Oncotarget. 2017 Jun 9;8(37):61475-61486. doi: 10.18632/oncotarget.18424. eCollection 2017 Sep 22.

Abstract

Runt-related transcription factor 3 (RUNX3) has been reported as a tumor suppressor in some kinds of cancers. In the present study, hepatocellular carcinoma (HCC) microarray analysis showed that RUNX3 expression was significantly lower in HCC tissues compared with that in adjacent non-tumor tissues, and was negatively associated with metastasis and TNM stage. RUNX3 was an independently prognostic factor for 5-year overall and disease-free patient survival. Mechanically, RUNX3 repressed metastasis and invasion of HCC, and increased E-cadherin expression. RUNX3 also repressed microRNA-186 to increase E-cadherin expression. We demonstrated that miR-186 mimics attenuated RUNX3-induced increase of E-cadherin and inhibition of metastasis and invasion. In conclusion, RUNX3 suppressed HCC cell migration and invasion by targeting the miR-186/E-cadherin/EMT pathway. RUNX3 may be recommended as an effective prognostic indicator and therapeutic target for patients with HCC.

摘要

runt相关转录因子3(RUNX3)在某些癌症中被报道为一种肿瘤抑制因子。在本研究中,肝细胞癌(HCC)芯片分析显示,与相邻非肿瘤组织相比,RUNX3在HCC组织中的表达显著降低,且与转移和TNM分期呈负相关。RUNX3是患者5年总生存率和无病生存率的独立预后因素。机制上,RUNX3抑制HCC的转移和侵袭,并增加E-钙黏蛋白的表达。RUNX3还通过抑制微小RNA-186来增加E-钙黏蛋白的表达。我们证明,miR-186模拟物减弱了RUNX3诱导的E-钙黏蛋白增加以及对转移和侵袭的抑制作用。总之,RUNX3通过靶向miR-186/E-钙黏蛋白/上皮-间质转化(EMT)途径抑制HCC细胞的迁移和侵袭。RUNX3可能被推荐作为HCC患者有效的预后指标和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c6c/5617438/c228aa11c59b/oncotarget-08-61475-g001.jpg

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