Wang Guihu, Popovic Branimir, Tao Junyan, Jiang An
National-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, Second Affiliated Hospital, Xi'an Jiaotong University Xi'an, Shaanxi, People's Republic of China.
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China Xi'an, Shaanxi, People's Republic of China.
Am J Cancer Res. 2020 May 1;10(5):1366-1383. eCollection 2020.
Cumulative evidence has indicated that mitochondrial respiration dysfunction plays important roles in tumorigenesis. However, the role of COX7RP, a critical regulator in the formation of mitochondrial respiratory supercomplex that has been suggested to be over-expressed in hepatocellular carcinoma (HCC) by our bioinformatic analysis of TCGA data, in tumor progression remains largely unclear. In this study, we found that COX7RP is frequently over-expressed in HCC mainly due to the down-regulation of miR-130a-3p and predicts poor prognosis of HCC patients. Functional experiments revealed that COX7RP promoted both growth and metastasis of HCC through induction of cell cycle progression and epithelial to mesenchymal transition (EMT), and suppression of cell apoptosis. Mechanistically, increased generation of reactive oxygen species (ROS) and subsequently activated nuclear transcription factor-κB (NF-κB) signaling was found to contribute to the promotion of HCC cell growth and metastasis by COX7RP. Collectively, COX7RP plays a critical oncogenic role in hepatocellular carcinogenesis, supporting COX7RP as a novel prognostic factor and therapeutic target in HCC.
越来越多的证据表明，线粒体呼吸功能障碍在肿瘤发生中起重要作用。然而，COX7RP作为线粒体呼吸超复合物形成中的关键调节因子，通过我们对TCGA数据的生物信息学分析表明其在肝细胞癌（HCC）中过表达，但其在肿瘤进展中的作用仍不清楚。在本研究中，我们发现COX7RP在HCC中经常过表达，主要是由于miR-130a-3p的下调，并预示着HCC患者的预后不良。功能实验表明，COX7RP通过诱导细胞周期进程和上皮-间质转化（EMT）以及抑制细胞凋亡，促进HCC的生长和转移。机制上，发现活性氧（ROS）生成增加以及随后激活的核转录因子-κB（NF-κB）信号通路有助于COX7RP促进HCC细胞的生长和转移。总的来说，COX7RP在肝细胞癌发生中起关键的致癌作用，支持COX7RP作为HCC的一种新的预后因素和治疗靶点。
