| First Author | Zhang G | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 8 | Pages | 107370 |
| PubMed ID | 37539028 | Mgi Jnum | J:338877 |
| Mgi Id | MGI:7515937 | Doi | 10.1016/j.isci.2023.107370 |
| Citation | Zhang G, et al. (2023) Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression. iScience 26(8):107370 |
| abstractText | 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-1alpha 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. |
