Nr3c2, also known as the mineralocorticoid receptor (MR), is a crucial nuclear receptor. It is involved in multiple biological processes, with its functions including regulation of salt and water balance, and it participates in various signaling pathways, such as those related to glucose metabolism, inflammation, and cell survival. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions [3].

In pancreatic cancer, MIF inhibits Nr3C2, and this MIF/NR3C2 axis regulates glucose metabolism reprogramming via MAPK-ERK and AP-1 pathways, influencing cancer growth and progression [1]. In invasive breast carcinoma, high NR3C2 expression is associated with better patient survival, and it may be related to pathways like neuroactive ligand-receptor interaction, focal adhesion, and ECM-receptor interaction [2]. In pseudohypoaldosteronism type 1A, NR3C2 microdeletions can cause the disease, highlighting its role in mineralocorticoid-related functions [3]. In coronary artery disease, NR3C2 promotes NLRP3-induced inflammatory responses in ox-LDL-induced human coronary endothelial cells [4]. In colorectal and colon cancer, NR3C2 inhibits cell proliferation, invasion, angiogenesis, and affects glucose metabolism and signaling pathways like Wnt/β-Catenin and AKT/ERK [5,6,7]. In ischemic cerebral infarction, NR3C2 activates LCN2 transcription, promoting endoplasmic reticulum stress and cell apoptosis [8]. In non-small cell lung cancer, NR3C2 is a potential diagnostic and prognostic biomarker and therapeutic target, with its low expression related to patient clinical indexes [9].

In conclusion, Nr3c2 plays essential roles in a variety of biological processes and is involved in multiple disease conditions, including cancer, cardiovascular, and endocrine-related diseases. The use of KO/CKO mouse models has significantly contributed to revealing these functions, helping us understand the molecular mechanisms underlying these diseases and potentially guiding the development of new therapeutic strategies.

References:

1. Yang, Shouhui, Tang, Wei, Azizian, Azadeh, Ambs, Stefan, Hussain, Perwez. . MIF/NR3C2 axis regulates glucose metabolism reprogramming in pancreatic cancer through MAPK-ERK and AP-1 pathways. In Carcinogenesis, 45, 582-594. doi:10.1093/carcin/bgae025. https://pubmed.ncbi.nlm.nih.gov/38629149/

2. Lu, Jianjun, Hu, Fang, Zhou, Yingling. 2021. NR3C2-Related Transcriptome Profile and Clinical Outcome in Invasive Breast Carcinoma. In BioMed research international, 2021, 9025481. doi:10.1155/2021/9025481. https://pubmed.ncbi.nlm.nih.gov/33564687/

3. Boyanton, Bobby L, Zarate, Yuri A, Broadfoot, Brannon G, Kelly, Thomas, Crawford, Brendan D. . NR3C2 microdeletions-an underrecognized cause of pseudohypoaldosteronism type 1A: a case report and literature review. In Laboratory medicine, 55, 640-644. doi:10.1093/labmed/lmae005. https://pubmed.ncbi.nlm.nih.gov/38493321/

4. Chen, Xiaofan, Li, Weidong, Chang, Chengdong. . NR3C2 mediates oxidised low-density lipoprotein-induced human coronary endothelial cells dysfunction via modulation of NLRP3 inflammasome activation. In Autoimmunity, 56, 2189135. doi:10.1080/08916934.2023.2189135. https://pubmed.ncbi.nlm.nih.gov/36919662/

5. Liu, Hui, Lei, Wenqi, Li, Zhigui, Wang, Xiaodong, Zhou, Liming. 2023. NR3C2 inhibits the proliferation of colorectal cancer via regulating glucose metabolism and phosphorylating AMPK. In Journal of cellular and molecular medicine, 27, 1069-1082. doi:10.1111/jcmm.17706. https://pubmed.ncbi.nlm.nih.gov/36950803/

6. Nie, Ke, He, Zhong-Jiang, Kong, Ling-Jun. 2024. NR3C2 affects the proliferation and invasiveness of colon cancer cells through the Wnt/β-Catenin signaling pathway. In Journal of cancer research and clinical oncology, 150, 411. doi:10.1007/s00432-024-05935-8. https://pubmed.ncbi.nlm.nih.gov/39237674/

7. Li, Jia, Xu, Zhao. 2022. NR3C2 suppresses the proliferation, migration, invasion and angiogenesis of colon cancer cells by inhibiting the AKT/ERK signaling pathway. In Molecular medicine reports, 25, . doi:10.3892/mmr.2022.12649. https://pubmed.ncbi.nlm.nih.gov/35191517/

8. Wang, Jianxiu, Jin, Jing, Li, Guozhong. 2023. NR3C2 activates LCN2 transcription to promote endoplasmic reticulum stress and cell apoptosis in ischemic cerebral infarction. In Brain research, 1822, 148632. doi:10.1016/j.brainres.2023.148632. https://pubmed.ncbi.nlm.nih.gov/37832761/

9. Sun, Yuan-Yuan, Gao, Hai-Cheng, Guo, Peng, Liu, Jin-Yi, Han, Fei. 2024. Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non-small cell lung cancer. In Cancer innovation, 3, e122. doi:10.1002/cai2.122. https://pubmed.ncbi.nlm.nih.gov/38948253/