Nr0b2, also known as Small Heterodimer Partner (SHP), is an orphan nuclear receptor that functions as a transcriptional regulator. It is involved in controlling various metabolic processes, such as cholesterol homeostasis, lipid metabolism, and lipophagy [1,3-5,7]. Nr0b2 is associated with pathways like TGF-β, Hedgehog, anti-apoptotic, and nuclear hormone receptor signaling pathways [6]. It plays a crucial role in maintaining physiological homeostasis and is of great significance in understanding disease mechanisms [1-7,9,10]. Genetic models, especially gene knockout (KO) mouse models, are valuable for studying Nr0b2's functions.

In a study on breast cancer, mice lacking Nr0B2 exhibited accelerated tumor growth, indicating that Nr0B2 impairs the expansion of regulatory T cells (Tregs) within myeloid cells, thereby reducing tumor growth [3]. In the context of primary sclerosing cholangitis, NR0B2 was upregulated in the liver, and its heterogeneity was found in cholangiocyte cell types, highlighting a metabolic and premalignant reprogramming of cholangiocytes [2]. For gastric diseases, bioinformatics analysis showed that NR0B2 expression levels were reduced in gastric cancer and increased in gastritis, and drug-target Mendelian randomization revealed its association with the risk of gastric diseases [1]. In liver cancer, NR0B2 expression was downregulated, and higher expression was associated with better relapse-free and progression-free survival, especially in Asian male patients with a viral infection history [4]. In non-alcoholic steatohepatitis, epiberberine upregulated SHP (NR0B2) to suppress hepatic triglyceride synthesis and improve liver steatosis [5].

In conclusion, Nr0b2 is a key regulator in multiple metabolic and disease-related processes. KO mouse models and other studies have revealed its role in cancer progression, gastric diseases, liver-related diseases, and immune-related processes. Understanding Nr0b2's functions provides potential therapeutic targets for various diseases, including cancer, gastric diseases, and non-alcoholic steatohepatitis.

References:

1. Li, Zhengwen, Xu, Lijia, Huang, Dongliang, Haenen, Guido R M M, Zhang, Ming. 2024. NR0B2 Is a Key Factor for Gastric Diseases: A GEO Database Analysis Combined with Drug-Target Mendelian Randomization. In Genes, 15, . doi:10.3390/genes15091210. https://pubmed.ncbi.nlm.nih.gov/39336801/

2. Desterke, Christophe, Chung, Chuhan, Pan, David, Azoulay, Daniel, Feray, Cyrille. 2022. Early Deregulation of Cholangiocyte NR0B2 During Primary Sclerosing Cholangitis. In Gastro hep advances, 2, 49-62. doi:10.1016/j.gastha.2022.07.023. https://pubmed.ncbi.nlm.nih.gov/39130146/

3. Vidana Gamage, Hashni Epa, Shahoei, Sayyed Hamed, Wang, Yu, Apetoh, Lionel, Nelson, Erik R. 2024. NR0B2 re-educates myeloid immune cells to reduce regulatory T cell expansion and progression of breast and other solid tumors. In Cancer letters, 597, 217042. doi:10.1016/j.canlet.2024.217042. https://pubmed.ncbi.nlm.nih.gov/38908543/

4. Zhu, Runzhi, Tu, Yanjie, Chang, Jingxia, Wang, Jinhu, Li, Benyi. 2021. The Orphan Nuclear Receptor Gene NR0B2 Is a Favorite Prognosis Factor Modulated by Multiple Cellular Signal Pathways in Human Liver Cancers. In Frontiers in oncology, 11, 691199. doi:10.3389/fonc.2021.691199. https://pubmed.ncbi.nlm.nih.gov/34055653/

5. Zhou, Li-Ming, Fan, Jin-Hua, Xu, Min-Min, Li, Xue-Gang, Ye, Xiao-Li. 2023. Epiberberine regulates lipid synthesis through SHP (NR0B2) to improve non-alcoholic steatohepatitis. In Biochimica et biophysica acta. Molecular basis of disease, 1869, 166639. doi:10.1016/j.bbadis.2023.166639. https://pubmed.ncbi.nlm.nih.gov/36638873/

6. Lam, Kuen Kuen, Sethi, Raman, Tan, Grace, Lai, Poh San, Cheah, Peh Yean. 2020. The orphan nuclear receptor NR0B2 could be a novel susceptibility locus associated with microsatellite-stable, APC mutation-negative early-onset colorectal carcinomas with metabolic manifestation. In Genes, chromosomes & cancer, 60, 61-72. doi:10.1002/gcc.22904. https://pubmed.ncbi.nlm.nih.gov/33094510/