Pla2g4f, a member of the phospholipase A2 superfamily, catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, and is involved in the arachidonic acid cascade [4]. It is associated with multiple biological processes including lipid metabolism-related pathways such as glycerophospholipid metabolism [2,5].

In triple-negative breast cancer (TNBC), it functions as a cell-autonomous metabolic reprogramming factor, promoting the proliferation, migration, and survival of TNBC cells in vitro, driven by dysregulated glucose and lipid metabolism, and mediated through the activation of the AKT/PI3K signaling pathway [1]. In mice deficient in glutathione peroxidases 1 and 2, Pla2g4f was identified as a likely colitis gene candidate, as it produces arachidonic acid which is metabolized by GPXs [3]. In chickens, its methylation level was negatively correlated with its expression, and it was identified as a key candidate gene influencing intramuscular fat deposition [2].

In summary, Pla2g4f plays crucial roles in lipid metabolism-related biological processes. Studies in mouse models and other organisms have revealed its significance in diseases like TNBC, colitis, and in processes such as intramuscular fat deposition. These findings contribute to understanding disease mechanisms and potential therapeutic targets related to Pla2g4f-associated pathways.

References:

1. Tang, Xun, Jiang, Ning, Kou, Yingying, Cheng, Shan, Yan, Feng. 2025. PLA2G4F is a metabolic checkpoint in triple-negative breast cancer: Insights from multiple omics analysis and experiments. In Molecular therapy. Oncology, 33, 200963. doi:10.1016/j.omton.2025.200963. https://pubmed.ncbi.nlm.nih.gov/40212962/

2. Zhu, Jinmei, Cai, Richun, Yu, Yang, Wang, Shubai, Cui, Huanxian. 2024. Integrative multiomics analysis identifies key genes regulating intramuscular fat deposition during development. In Poultry science, 103, 104404. doi:10.1016/j.psj.2024.104404. https://pubmed.ncbi.nlm.nih.gov/39447331/

3. Esworthy, R Steven, Kim, Byung-Wook, Rivas, Guillermo E, Doroshow, James H, Chu, Fong-Fong. 2012. Analysis of candidate colitis genes in the Gdac1 locus of mice deficient in glutathione peroxidase-1 and -2. In PloS one, 7, e44262. doi:10.1371/journal.pone.0044262. https://pubmed.ncbi.nlm.nih.gov/22970191/

4. Recuero, Saulo da Cunha, Viana, Nayara I, Reis, Sabrina T, Srougi, Miguel, Leite, Katia R M. 2024. Phospholipase A2 expression in prostate cancer as a biomarker of good prognosis: A comprehensive study in patients with long follow-up. In Urologia, 91, 720-726. doi:10.1177/03915603241257362. https://pubmed.ncbi.nlm.nih.gov/39051490/

5. Hong, Longsheng, Sun, Zongyi, Xu, Danning, Tian, Yunbo, Li, Bingxin. 2023. Transcriptome and lipidome integration unveils mechanisms of fatty liver formation in Shitou geese. In Poultry science, 103, 103280. doi:10.1016/j.psj.2023.103280. https://pubmed.ncbi.nlm.nih.gov/38042038/