Pmepa1, also known as prostate transmembrane protein androgen induced 1, is an androgen-responsive gene. It serves as an essential regulator of multiple signaling pathways, such as androgen and TGF-β signaling in solid tumors. PMEPA1 has five isoforms with distinct extracellular domains, and specific motifs in its cytoplasmic domain mediate isoform-specific functions through protein-protein interactions [1].

In hepatocellular carcinoma (HCC), overexpression of MYC + PMEPA1 in a genetically engineered mouse model led to HCC development in about 60% of mice, with decreased survival compared to mice overexpressing MYC alone. This demonstrated the oncogenic role of PMEPA1 in HCC, as it was linked to TGF-β activation, immune exhaustion, and an aggressive phenotype [2]. In osteomyelitis, knockdown of Pmepa1 in a rat model alleviated SpA-induced pyroptosis and osteogenic differentiation inhibition of human bone marrow mesenchymal stem cells (hBMSCs) by downregulating the p38MAPK/NLRP3 signaling axis, suggesting that modulating Pmepa1 expression may be a potential strategy for treating osteomyelitis [3].

In conclusion, Pmepa1 is a key regulator of multiple signaling pathways. Its study using mouse models has revealed its oncogenic role in HCC and its potential as a therapeutic target in osteomyelitis. These findings enhance our understanding of disease pathogenesis and may open new avenues for targeted therapeutic interventions.

References:

1. Sharad, Shashwat, Dobi, Albert, Srivastava, Shiv, Srinivasan, Alagarsamy, Li, Hua. 2020. PMEPA1 Gene Isoforms: A Potential Biomarker and Therapeutic Target in Prostate Cancer. In Biomolecules, 10, . doi:10.3390/biom10091221. https://pubmed.ncbi.nlm.nih.gov/32842649/

2. Piqué-Gili, Marta, Andreu-Oller, Carmen, Mesropian, Agavni, Pinyol, Roser, Llovet, Josep M. 2024. Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC. In JHEP reports : innovation in hepatology, 6, 101212. doi:10.1016/j.jhepr.2024.101212. https://pubmed.ncbi.nlm.nih.gov/39524206/

3. Li, Mingjun, Shi, Xiangwen, Wu, Yipeng, Zhang, Bihuan, Xu, Yongqing. 2023. Pmepa1 knockdown alleviates SpA-induced pyroptosis and osteogenic differentiation inhibition of hBMSCs via p38MAPK/NLRP3 axis. In International immunopharmacology, 124, 110843. doi:10.1016/j.intimp.2023.110843. https://pubmed.ncbi.nlm.nih.gov/37634444/