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冠蛋白6通过增强经典Wnt/β-连环蛋白信号通路促进肝细胞癌进展。

Coronin 6 promotes hepatocellular carcinoma progression by enhancing canonical Wnt/beta-catenin signaling pathway.

作者信息

Zhang Jing, Li Pengfei, Li Ting, Zhou Zhiqin, Wu Huiling, Zhang Lei

机构信息

Department of Plastic and Aesthetic Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

School of Medicine, Zhejiang University, Hangzhou, 310058, China.

出版信息

J Cancer. 2021 Nov 4;12(24):7465-7476. doi: 10.7150/jca.62873. eCollection 2021.

Abstract

Hepatocellular carcinoma (HCC), which is one of the most commonly diagnosed cancers, accounts for a large majority of cancer-related mortality worldwide. Although various genes have already been found to play vital regulatory roles in HCC progression, the pathological mechanism is still not well-understood. In this study, we find Coronin 6 (CORO6) is highly expressed in HCC samples with higher grades and is correlated with poor patient outcomes. CORO6 depletion significantly impairs the cell survival, migratory and invasive abilities of HCC cells. Pathway analysis and reporter assay reveal that Wnt signaling is enhanced by CORO6 in HCC cells. Moreover, is identified as a target gene of CORO6. experiments suggest that knockdown of CORO6 inhibited the tumor growth. Importantly, expression of the key WNT target genes that are involved in cell cycle regulation and tumorigenesis, is downregulated in the absence of CORO6. Collectively, our results uncover a novel function of CORO6 in HCC progression and prove that the activation of WNT signaling is responsible for the tumor-promoting role of CORO6, which may offer a new target for therapeutic gain of treating HCC.

摘要

肝细胞癌(HCC)是最常被诊断出的癌症之一,在全球癌症相关死亡率中占很大比例。尽管已经发现多种基因在HCC进展中发挥重要的调节作用,但其病理机制仍未被充分理解。在本研究中,我们发现冠蛋白6(CORO6)在高分级的HCC样本中高表达,且与患者的不良预后相关。CORO6缺失显著损害HCC细胞的存活、迁移和侵袭能力。通路分析和报告基因检测表明,CORO6在HCC细胞中增强了Wnt信号传导。此外, 被鉴定为CORO6的靶基因。 实验表明,敲低CORO6可抑制肿瘤生长。重要的是,在缺乏CORO6的情况下,参与细胞周期调控和肿瘤发生的关键WNT靶基因的表达下调。总体而言,我们的结果揭示了CORO6在HCC进展中的新功能,并证明WNT信号传导的激活是CORO6促肿瘤作用的原因,这可能为HCC治疗提供一个新的治疗靶点。

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