Rcan2, short for regulator of calcineurin 2, is a gene that plays significant roles in multiple biological processes. It is involved in regulating the calcineurin-nuclear factor of activated T cells signaling pathway [4]. It has been associated with important physiological functions such as body weight regulation, tumor progression, and bone development, highlighting its overall biological importance. Genetic models, like mouse models, have been crucial for studying its functions [3,4].

In mouse models, inactivation of the Rcan2 gene led to a reduction in food intake, which in turn ameliorated age-and diet-induced obesity, indicating its role in body weight regulation [3]. Also, Rcan2 -/- mice displayed an isolated defect in osteoblast function, with delayed intramembranous ossification, impaired cortical bone formation during development, and increased mineralization in adult bone [4]. In gastric carcinoma, RCAN2-positive GCs were more advanced in TNM classification and tumour stage, and RCAN2 was an independent prognostic classifier. RCAN2 siRNA inhibited cell growth, invasiveness, and phosphorylation of AKT and p44/p42 (ERK1/2) in GC cell lines [1]. In colorectal cancer, RCAN2 was poorly expressed in cancer tissues and cells, especially in cancer stem cells (CSCs). Its restoration reduced the stemness of CSCs by blocking the calcineurin-NFATC1 signal transduction [2].

In conclusion, Rcan2 has diverse essential biological functions. Mouse gene knockout models have revealed its roles in body weight regulation, bone development, and cancer-related processes such as tumor progression and stem cell property regulation in gastric and colorectal cancers. These findings contribute to our understanding of the mechanisms underlying obesity and cancer, potentially providing new insights for treatment strategies in these disease areas.

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. Chang, Yunli, Chen, Lingling, Tang, Jie, Ji, Jieru, Xu, Ming. 2023. USP7-mediated JUND suppresses RCAN2 transcription and elevates NFATC1 to enhance stem cell property in colorectal cancer. In Cell biology and toxicology, 39, 3121-3140. doi:10.1007/s10565-023-09822-9. https://pubmed.ncbi.nlm.nih.gov/37535148/

3. Sun, Xiao-yang, Hayashi, Yoshitaka, Xu, Sai, Tang, Ya-ping, Murata, Yoshiharu. 2011. Inactivation of the Rcan2 gene in mice ameliorates the age- and diet-induced obesity by causing a reduction in food intake. In PloS one, 6, e14605. doi:10.1371/journal.pone.0014605. https://pubmed.ncbi.nlm.nih.gov/21298050/

4. Bassett, J H Duncan, Logan, John G, Boyde, Alan, Murata, Yoshiharu, Williams, Graham R. 2012. Mice lacking the calcineurin inhibitor Rcan2 have an isolated defect of osteoblast function. In Endocrinology, 153, 3537-48. doi:10.1210/en.2011-1814. https://pubmed.ncbi.nlm.nih.gov/22593270/