CRIF1 overexpression facilitates tumor growth and metastasis through inducing ROS/NFκB pathway in hepatocellular carcinoma
CRIF1 overexpression facilitates tumor growth and metastasis through inducing ROS/NFκB pathway in hepatocellular carcinoma
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CRIF1过表达通过诱导肝细胞癌中的ROS/NFκB通路促进肿瘤生长和转移
DOI：
10.1038/s41419-020-2528-7
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发表时间：
2020-05-07
影响因子：
9
通讯作者：
Liu, Chang
中科院分区：
文献类型：
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作者：
Chang, Hulin;Li, Juntang;Liu, Chang
CR 6相互作用因子1（Crif 1）是氧化磷酸化（OXPHOS）复合物组装所需的线粒体蛋白。我们基于癌症基因组图谱（TCGA）数据库的生物信息学分析揭示了CRIF 1在肝细胞癌（HCC）中的异常过表达。然而，CRIF 1在该恶性肿瘤中的临床意义和生物学功能尚不清楚。在这里，我们报告了CRIF 1在HCC细胞中经常过表达，主要是由于miR-497- 5 p的下调，这与HCC患者的预后不良有关。CRIF 1通过抑制细胞凋亡和诱导细胞周期进展以及上皮向间质转化（EMT）促进HCC生长和转移。从机制上讲，发现线粒体ROS产生增加以及随后NF κ B信号通路的激活参与了CRIF 1在HCC细胞中促进生长和转移。总之，CRIF 1通过激活ROS/NF κ B通路在HCC进展中发挥致癌作用，这意味着CRIF 1是HCC的潜在预后因子和治疗靶点。
CR6-interacting factor 1 (Crif1) is a mitochondrial protein which is required for the assembly of oxidative phosphorylation (OXPHOS) complexes. Our bioinformatics analysis based on Cancer Genome Atlas (TCGA) database revealed an aberrant overexpression of CRIF1 in hepatocellular carcinoma (HCC). However, the clinical significance and biological functions of CRIF1 are still unclear in this malignancy. Here, we report that CRIF1 is frequently overexpressed in HCC cells mainly due to the downregulation of miR-497-5p, which is associated with poor prognosis of patients with HCC. CRIF1-promoted HCC growth and metastasis by suppressing cell apoptosis and inducing cell cycle progression and epithelial to mesenchymal transition (EMT). Mechanistically, increased mitochondrial ROS production and consequently activation of the NF kappa B signaling pathway was found to be involved in the promotion of growth and metastasis by CRIF1 in HCC cells. In summary, CRIF1 plays an oncogenic role in HCC progression through activating ROS/NFKB pathway, implying CRIF1 as a potential prognostic factor and therapeutic target in HCC.