Chrm3, encoding the muscarinic acetylcholine receptor M3, is a key gene involved in various physiological and pathological processes. The M3 receptor is one of the well-characterized receptors of pancreatic β cells, regulating insulin secretion, and is also associated with signal transduction pathways related to cell proliferation, apoptosis, and inflammation [3].

In a severe acute pancreatitis mice model, Chrm3 was upregulated in pancreatitis. Reduction of Chrm3 decreased the pathological lesion of severe acute pancreatitis and reduced amylase activities in serum. Chrm3 could suppress acinar cells necrosis, at least in part by stabilizing caspase-8 [3]. In another study on L-arginine-induced severe acute pancreatitis, CHRM3 was activated and regulated the disease through the mitogen-activated protein kinase/p38 pathway, promoting necrosis via the MAPK-p38/miR-31-5p/RIP3 axis [4]. In glioblastoma, high levels of CHRM3 correlated with poor prognosis. Knockdown of CHRM3 inhibited GBM cell growth and invasion, and suppressed GBM progression in an orthotopic GBM animal model, suggesting its role in promoting glioblastoma progression via activation of oncogenic invasive growth factors [2]. Also, in colon cancer, the proliferative effects of bile acids on colon epithelium may be through interaction with CHRM3, and CHRM3-associated miRNAs might play a role in bile-acid-induced proliferation of H508 colon cancer cells [1].

In conclusion, Chrm3 plays crucial roles in multiple disease conditions, especially in pancreatitis and certain cancers. Studies using gene knockout or knockdown models in mice have been instrumental in revealing its functions in these diseases, such as its role in regulating cell death in pancreatitis and promoting cancer cell growth and invasion. These findings provide valuable insights into the molecular mechanisms underlying these diseases and potential therapeutic targets related to Chrm3 [1,2,3,4].

References:

1. Aktan, Çağdaş, Tekin, Fatih, Oruç, Nevin, Özütemiz, Ömer. . CHRM3-Associated miRNAs May Play a Role in Bile Acid-Induced Proliferation of H508 Colon Cancer Cells. In The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 34, 298-307. doi:10.5152/tjg.2022.22605. https://pubmed.ncbi.nlm.nih.gov/36919835/

2. Zhang, Bin, Zhao, Jianyi, Wang, Yongzhi, Zhang, Junchen, Meng, Wei. 2023. CHRM3 is a novel prognostic factor of poor prognosis and promotes glioblastoma progression via activation of oncogenic invasive growth factors. In Oncology research, 31, 917-927. doi:10.32604/or.2023.030425. https://pubmed.ncbi.nlm.nih.gov/37744266/

3. Huang, Ning, Murtaza, Ghulam, Wang, Lujing, Ma, Ning, Gao, Xu. 2019. Chrm3 protects against acinar cell necrosis by stabilizing caspase-8 expression in severe acute pancreatitis mice model. In Journal of cellular biochemistry, 121, 2618-2631. doi:10.1002/jcb.29483. https://pubmed.ncbi.nlm.nih.gov/31692054/

4. Luan, Jing, Kou, Jiayuan, Huang, Ning, Gao, Xu, Ma, Ning. . Inhibition of CHRM3 Alleviates Necrosis Via the MAPK-p38/miR-31-5p/RIP3 Axis in L-Arginine-Induced Severe Acute Pancreatitis. In Pancreas, 49, 1335-1341. doi:10.1097/MPA.0000000000001684. https://pubmed.ncbi.nlm.nih.gov/33122522/