CircCOCH 通过调节 miR-450a 和激活 PI3K/mTOR 通路在肝细胞癌中发挥关键作用

IF 5 2区 医学 Q2 Medicine
Weiwei Jiang , Yan Wang , Wanli He , Peng Wang , Peng Meng , Shanfeng Zhang
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引用次数: 0

摘要

肝细胞癌(HCC)是一种原发性肝癌,致病性强,预后极差。环状 RNA(circRNA)在 HCC 癌变和进展中的作用仍有待确定。基于对 HCC 相关数据库的分析,以及对 25 例 HCC 患者组织和 HCC 细胞系的表达分析和鉴定,我们发现 hsa_circ_0031431 (circCOCH) 在 HCC 组织和细胞系中显著高表达。circCOCH 的高表达与肿瘤增殖和转移的增强有关,而敲除 circCOCH 可以抑制 HCC 在体内和体外的生长。机理研究表明,circCOCH通过海绵miR-450a上调表皮生长因子受体(EGFR)的表达,从而激活磷酸肌醇3-激酶(PI3Ks)细胞通路,促进HCC的增殖和转移。此外,我们还发现 IGF2BP3 介导了 circCOCH 的生物生成。本研究对 circRNAs 在 HCC 癌变病因学中的作用提供了新的见解,并可能成为治疗 HCC 的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CircCOCH plays a critical role in Hepatocellular carcinoma through modulating miR-450a and activating PI3K/mTOR pathway

Hepatocellular carcinoma (HCC) is a primary liver cancer with high pathogenicity and extremely poor prognosis. The role of circular RNAs (circRNAs) in HCC carcinogenesis and progression remains to be determined. Based on the analysis of HCC-related databases, as well as the expression analysis and identification of 25 HCC patient tissues and HCC cell lines, we found that the hsa_circ_0031431 (circCOCH) is significantly highly expressed in HCC tissues and cell lines. High circCOCH expression is associated with enhanced tumor proliferation and metastasis, and knocking down circCOCH can inhibit the growth of HCC in vivo and in vitro. Mechanistic studies show that circCOCH upregulates the expression of epidermal growth factor receptor (EGFR) through sponge miR-450a, thereby activating the Phosphoinositide 3-kinases (PI3Ks) cell pathway to promote HCC proliferation and metastasis. Futhermore, we found that IGF2BP3 mediates the biogenesis of circCOCH. The present study provides innovative insights into the role of circRNAs in the etiology of HCC carcinogenesis and might serve as a new promising therapeutic target for HCC.

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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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