Rcan2, or regulator of calcineurin 2, is a physiological inhibitor of the calcineurin-nuclear factor of activated T cells signaling pathway, which controls the differentiation and function of osteoclasts and osteoblasts. It also seems to be involved in regulating food intake and energy balance, potentially influencing body weight regulation [2,4].

In gastric cancer, RCAN2-positive tumors were more advanced in TNM classification and tumour stage, and RCAN2 was an independent prognostic classifier. RCAN2 siRNA-transfected GC cell lines had reduced cell growth and invasiveness, and RCAN2 siRNA inhibited the phosphorylation of AKT and p44/p42 (ERK1/2) [1]. In female mice, Rcan2 promotes weight gain, but this effect is attenuated by 17β-estradiol-mediated energy expenditure, suggesting they regulate body weight through different mechanisms [2]. In hepatocellular carcinoma, RCAN2 promotes apoptosis via upregulating the EHF/DR5 pathway, and its high expression is correlated with better overall survival [3].

In summary, Rcan2 plays crucial roles in various biological processes and disease conditions. Its function in promoting tumor progression in gastric cancer, regulating body weight in mice, and promoting apoptosis in hepatocellular carcinoma has been revealed through model-based research. These findings contribute to understanding the mechanisms of these diseases and potentially offer new therapeutic targets.

References:

1. Hattori, Yui, Sentani, Kazuhiro, Shinmei, Shunsuke, Ohdan, Hideki, Yasui, Wataru. . Clinicopathological significance of RCAN2 production in gastric carcinoma. In Histopathology, 74, 430-442. doi:10.1111/his.13764. https://pubmed.ncbi.nlm.nih.gov/30307052/

2. Ding, Ling-Cui, Gong, Qian-Qian, Li, Shi-Wei, Gao, Jian-Gang, Sun, Xiao-Yang. . Rcan2 and estradiol independently regulate body weight in female mice. In Oncotarget, 8, 48098-48109. doi:10.18632/oncotarget.18259. https://pubmed.ncbi.nlm.nih.gov/28624805/

3. Xu, Yu-Jie, Lai, Zhi-Cheng, Kan, Anna, Zhang, Shuai, He, Min-Ke. . TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma. In Frontiers in bioscience (Landmark edition), 29, 243. doi:10.31083/j.fbl2907243. https://pubmed.ncbi.nlm.nih.gov/39082336/

4. Wang, Hongya, Fang, Xia, Ren, Qian, Fan, Jiahao, Xu, Yong. 2022. Association Between Circulating Regulator of Calcineurin 2 Concentrations With Overweight and Obesity. In Frontiers in endocrinology, 13, 857841. doi:10.3389/fendo.2022.857841. https://pubmed.ncbi.nlm.nih.gov/35733783/