Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression

oleh: Guimin Zhang, Binrui Liu, Yun Yang, Shuo Xie, Lingcheng Chen, Hui Luo, Jian Zhong, Yinhao Wei, Fengzhu Guo, Jia Gan, Fan Zhu, Lin Xu, Qiqi Li, Yuge Shen, Huajin Zhang, Yan Liu, Rong Li, Hongxin Deng, Hanshuo Yang

Format: Article
Diterbitkan: Elsevier 2023-08-01

Deskripsi

Summary: Mitochondria play important roles in angiogenesis. However, the mechanisms remain elusive. In this study, we found that mitochondrial ubiquinol-cytochrome c reductase complex assembly factor 3 (UQCC3) is a key regulator of angiogenesis. TALEN-mediated knockout of Uqcc3 in mice caused embryonic lethality at 9.5–10.5 days postcoitum, and vessel density was dramatically reduced. Similarly, knockout of uqcc3 in zebrafish induced lethality post-fertilization and impaired vascular development. Knockout of UQCC3 resulted in slower tumor growth and angiogenesis. Mechanistically, UQCC3 was upregulated under hypoxia, promoted reactive oxygen species (ROS) generation, enhanced HIF-1α stability and increased VEGF expression. Finally, higher expression of UQCC3 was associated with poor prognosis in multiple types tumors, implying a role for UQCC3 in tumor progression. In conclusion, our findings highlight the important contribution of UQCC3 to angiogenesis under both physiological and pathological conditions, indicating the potential of UQCC3 as a therapeutic target for cancer.