Knockdown of NDUFC1 inhibits cell proliferation, migration, and invasion of hepatocellular carcinoma

作者：Fang Han, Junwei Liu, Hongwu Chu, Dan Cao, Jia Wu, Hong Fu, Anyang Guo, Weiqin Chen, Yingping Xu, Xiangdong Cheng, Yuhua Zhang · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.860084 · 被引用次数：14 · 研究领域：Coenzyme Q10 studies and effects、Mitochondrial Function and Pathology、Antioxidant Activity and Oxidative Stress

Background: NADH: ubiquinone oxidoreductase subunit C1(NDUFC1) encodes a subunit of the Complex I, which may support the structural stability of Complex I and assist in its biogenesis. The expression and functional roles of NDUFC1 in hepatocellular carcinoma (HCC) remain unknown. Result: . MTT assay determined that downregulation of NDUFC1 significantly inhibited cell proliferation. Flow cytometry with (propidium iodide) PI staining indicated silencing of NDUFC1 arrested cell cycle of BEL-7404 cells at G2 phase and SK-HEP-1 cells at S/G2 phase. Annexin V-PI double staining and flow cytometric analysis showed that the downregulation of NDUFC1 significantly increased the population of apoptotic cells. Wound-healing assay and transwell assay indicated that the downregulation of NDUFC1 suppressed the migration and invasion of HCC cells. According to the detection of complex1 activity, we found that the activity of NDUFC1 silenced group decreased, whereas the content of ROS increased. Furthermore, combined with bioinformatics analysis of senescence-related genes, we found that the silence of NDUFC1 in HCC could induce senescence and inhibit autophagy. In addition, NDUFC1 could correlate positively with cancer-related pathways, among which the p53 pathways and the PI3K/Akt/mTOR pathways. Finally, NDUFC1 is high expression in HCC specimens. High NDUFC1 expression was associated with poor prognosis and was an independent risk factor for reduced overall survival (OS). Conclusions: Our...