武漢大學朱帆研究組發現HBV相關HCC炎癌轉化過程中重要趨化因子

3月27日，國際學術期刊Clinical Cancer Research在線發表了武漢大學病毒學國家重點實驗室朱帆課題組的研究論文CKLF1 Enhances Inflammation-mediated Carcinogenesisand Prevents Doxorubicin-induced Apoptosis via IL-6/STAT3 Signaling in HCC（《CKLF1通過IL-6/STAT3信號通路誘導原發性肝癌中的炎癌轉化以及抑制多柔比星誘導的細胞凋亡》）。

病毒在癌症的發展中起著重要作用，多達15%的人類癌症都歸因於慢性病毒感染，如乙肝病毒（HBV）的感染。HBV感染導致的慢性炎症是肝癌的重要危險因素之一，90%的原發性肝細胞癌（HCC）患者主要由慢性肝損傷和炎症發展而來，而趨化因子與HCC尤其是HBV相關的HCC的關係，是近年來炎癌轉化機制研究的重點與熱點。

在朱帆教授的指導下，博士研究生柳又禕發現並證實人趨化素樣因子1 （CKLF1）是炎癌轉化過程中的一種重要的趨化因子。課題組發現CKLF1能被HBV上調，在HBV相關HCC組織中明顯高表達，並與原發性肝細胞癌的進程及不良預後密切相關。進一步研究發現CKLF1能通過IL-6/STAT3信號通路抑制經典抗癌藥物多柔比星對肝癌細胞的凋亡作用。該研究揭示了CKLF1在HBV相關HCC中所扮演的重要角色，為CKLF1在HBV炎癌轉化過程的機制研究打下了基礎，為HCC的耐藥性研究及靶向治療提供了新的思路。

Abstract

Purpose:Hepatocellular carcinoma (HCC), one of the most common and deadliest malignancies worldwide, has a poor prognosis, owing to its high potential for vascular invasion and metastasis and the lack of biomarkers for early diagnosis. Thus, it must be a crucial factor for investigating therapeutic strategies for HCC to identify the functional molecular targets. Here, we reported a novel chemokine, CKLF1, that might act as a pivotal modulator in the invasion and metastasis of HCC and could serve as an attractive target for cancer therapy.

Experimental Design:Bioinformatics analysis, PCR, Western blotting, and IHC were performed to detect the expression of CKLF1 in HCC. The function of CKLF1 was demonstrated by a series of in vitro and in vivo experiments. Pharmacologic treatment, flow cytometry, and Western blotting were carried out to demonstrate the potential mechanisms of CKLF1.

Results:We proved that CKLF1 was overexpressed in HCC tissues and was related to tumor stage, vascular invasion, and patient survival. Then, functional assays showed that CKLF1 promoted hepatocellular carcinogenesis and metastatic potential. Finally, the IL6/STAT3 signaling pathway was involved in the mechanistic investigation. The results demonstrated that CKLF1 enhanced the progression of HCC and prevented doxorubicin-induced apoptosis through activating the IL6/STAT3 pathway.

Conclusions:These data showed that CKLF1 inhibited apoptosis and promoted malignant transformation through the IL6/STAT3 pathway, and ultimately enhanced the development and metastasis of HCC. Thus, our work revealed that CKLF1 was a significant prognostic factor of HCC and might be a potential molecular therapeutic target for HCC.

本期編輯:Tony

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