Mapk12, also known as p38γ, is a member of the p38 MAPK family. It is involved in multiple cellular processes including proliferation, differentiation, apoptosis, stress responses, and cancer development [2,5,6]. It has been associated with pathways such as those regulating inflammation and the tumor immune microenvironment [2,4]. Genetic models, especially KO/CKO mouse models, can be valuable for further exploring its functions.

In osteoarthritis (OA), downregulation of Mapk12 was observed in H2O2-or IL-1β-stimulated cells and OA-related tissues. Over-expression of Mapk12 promoted cell proliferation and cartilage anabolism, inhibited cell senescence and cartilage catabolism, and relieved joint pain in relevant cell models and DMM mice, suggesting its role in modulating chondrocyte senescence in OA [1]. In cancer, Mapk12 was overexpressed in multiple cancer types, and its upregulated mRNA expression was related to a worse prognosis. Cytotoxicity and EdU experiments in THCA cells showed that Mapk12 knockdown inhibited cell proliferation. It was also closely related to the immune checkpoint, microsatellite instability, and tumor mutational burden, affecting tumor sensitivity to immunotherapy [2]. In ovine ovarian granulosa cells, high prolactin concentrations promoted apoptosis and inhibited steroid hormone secretion by upregulating Mapk12 through reducing L-PRLR and S-PRLR [3].

In conclusion, Mapk12 plays crucial roles in various biological processes and disease conditions. Model-based research, especially through KO/CKO mouse models, could potentially further clarify its functions. In OA, it is involved in chondrocyte senescence; in cancer, it impacts cell proliferation and the tumor immune microenvironment; and in ovine ovarian granulosa cells, it is related to apoptosis and steroid hormone regulation.

References:

1. Geng, Nana, Xian, Menglin, Deng, Lin, Bai, Zhixun, Guo, Fengjin. 2024. Targeting the senescence-related genes MAPK12 and FOS to alleviate osteoarthritis. In Journal of orthopaedic translation, 47, 50-62. doi:10.1016/j.jot.2024.06.008. https://pubmed.ncbi.nlm.nih.gov/39007035/

2. Wang, Jinju, Song, Zhe, Ren, Li, Gu, Yi, Feng, Chao. 2022. Pan-cancer analysis supports MAPK12 as a potential prognostic and immunotherapeutic target in multiple tumor types, including in THCA. In Oncology letters, 24, 445. doi:10.3892/ol.2022.13565. https://pubmed.ncbi.nlm.nih.gov/36420075/

3. Yang, Ruochen, Duan, Chunhui, Zhang, Shuo, Liu, Yueqin, Zhang, Yingjie. 2023. Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression of MAPK12 Gene. In International journal of molecular sciences, 24, . doi:10.3390/ijms241210269. https://pubmed.ncbi.nlm.nih.gov/37373417/

4. Escós, Alejandra, Diaz-Mora, Ester, Pattison, Michael, Ley, Steven C, Cuenda, Ana. 2023. p38γ and p38δ modulate innate immune response by regulating MEF2D activation. In eLife, 12, . doi:10.7554/eLife.86200. https://pubmed.ncbi.nlm.nih.gov/37458356/

5. Phan, Thuy, Zhang, Xu Hannah, Rosen, Steven, Melstrom, Laleh G. 2023. P38 kinase in gastrointestinal cancers. In Cancer gene therapy, 30, 1181-1189. doi:10.1038/s41417-023-00622-1. https://pubmed.ncbi.nlm.nih.gov/37248432/

6. Liu, Yue, Zhang, Han, Zhao, Shu, Zhang, Yue. 2024. A retrospective analysis of the clinicopathological features and prognostic value of MAPK12 protein expression in diffuse large B-cell lymphoma. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 26, 2966-2978. doi:10.1007/s12094-024-03515-3. https://pubmed.ncbi.nlm.nih.gov/38773060/