Cox6b2 is a component of cytochrome c oxidase (complex IV). It is mainly involved in oxidative phosphorylation (OXPHOS), a key metabolic pathway that generates ATP, the cell's energy currency. This gene is also associated with several biological processes such as cell proliferation, cell cycle regulation, and maintaining cell stemness [1,2,3,4,5]. Genetic models, like knockout mouse models, can be crucial for studying its function.

In a knockout (KO) mouse model of Cox6b2, male mice showed subfertility due to low sperm motility, though mitochondrial function measured by oxygen consumption rates was normal. This indicates that Cox6b2 is important for sperm motility and male fertility [6]. In various cancer studies, knockdown of Cox6b2 in lung adenocarcinoma, pancreatic ductal cancer, and gastric cancer cells led to decreased cell proliferation, metastasis, and altered cell cycle progression. In lung adenocarcinoma, it was part of an OXPHOS-related gene signature. In pancreatic ductal cancer, it enhanced OXPHOS function to promote metastasis. In gastric cancer, its high expression was associated with poor prognosis and promoted cell proliferation by inhibiting p53 signaling [1,2,3,5,7]. In trophoblast stem cells, RNA interference of Cox6b2 decreased mitochondrial Complex IV activity, ATP production, and self-renewal capacity, leading to differentiation [4].

In conclusion, Cox6b2 is essential for multiple biological functions, especially those related to energy metabolism through OXPHOS. Its role in sperm motility and male fertility is demonstrated by the Cox6b2 KO mouse model. In cancer, it promotes cell proliferation, metastasis, and cell cycle progression, highlighting its potential as a therapeutic target in oncology. The study of Cox6b2 using genetic models has provided valuable insights into its functions in both normal and disease-related biological processes.

References:

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2. Cheng, Chun-Chun, Wooten, Joshua, Gibbs, Zane A, Mishra, Prashant, Whitehurst, Angelique W. 2020. Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma. In eLife, 9, . doi:10.7554/eLife.58108. https://pubmed.ncbi.nlm.nih.gov/32990599/

3. Nie, Ke, Li, Jin, He, Xujun, Fang, Hezhi, Jin, Liqin. 2020. COX6B2 drives metabolic reprogramming toward oxidative phosphorylation to promote metastasis in pancreatic ductal cancer cells. In Oncogenesis, 9, 51. doi:10.1038/s41389-020-0231-2. https://pubmed.ncbi.nlm.nih.gov/32415061/

4. Saha, Sarbani, Bose, Rumela, Chakraborty, Shreeta, Ain, Rupasri. . Tipping the balance toward stemness in trophoblast: Metabolic programming by Cox6B2. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36, e22600. doi:10.1096/fj.202200703RR. https://pubmed.ncbi.nlm.nih.gov/36250984/

5. Shen, M, Zhao, N, Deng, X, Deng, M. . [High expression of COX6B2 in gastric cancer is associated with poor long-term prognosis and promotes cell proliferation and cell cycle progression by inhibiting p53 signaling]. In Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 44, 289-297. doi:10.12122/j.issn.1673-4254.2024.02.11. https://pubmed.ncbi.nlm.nih.gov/38501414/

6. Shimada, Keisuke, Lu, Yonggang, Ikawa, Masahito. 2023. Disruption of testis-enriched cytochrome c oxidase subunit COX6B2 but not COX8C leads to subfertility. In Experimental animals, 73, 1-10. doi:10.1538/expanim.23-0055. https://pubmed.ncbi.nlm.nih.gov/37423748/

7. Xu, Zihao, Wu, Zilong, Zhang, Jingtao, Yang, Pingliang, Yu, Bentong. 2020. Development and validation of an oxidative phosphorylation-related gene signature in lung adenocarcinoma. In Epigenomics, 12, 1333-1348. doi:10.2217/epi-2020-0217. https://pubmed.ncbi.nlm.nih.gov/32787683/