Calcb, also known as calcitonin-related polypeptide β, is a gene encoding a secretory neuropeptide. The peptide signals via the CGRP (calcitonin gene-related peptide) receptor complex, with RAMP1 being crucial for receptor specificity. Calcb is involved in multiple biological processes and has been associated with various diseases, suggesting its important role in maintaining normal physiological functions [1].

In a study of Ewing sarcoma (EwS), it was found that CALCB is specifically and highly overexpressed in EwS, and its expression is tightly linked to that of EWSR1-FLI1. Long-term knockdown of CALCB decreased EwS growth in vitro and in vivo, and knockdown of RAMP1 also reduced clonogenic/spheroidal growth and tumorigenicity. This indicates that targeting the CALCB/RAMP1 axis may be a new therapeutic strategy for EwS [1].

In another study, the methylation of CALCB in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer, and under this condition, p-AKT and p-CREB levels were decreased [2]. Also, in type 1 autoimmune pancreatitis, novel missense splice region variants of CALCB were identified, and in vitro, these mutants displayed decreased βCGRP and ERK1/2 phosphorylation [3]. Moreover, in salivary adenoid cystic carcinoma, the CALCB rs2839222 T/T genotype was closely related to the occurrence of the carcinoma, and serum CGRP and βCGRP could be used as novel markers [4].

In conclusion, Calcb plays a significant role in various disease conditions, such as Ewing sarcoma, pancreatic ductal adenocarcinoma, type 1 autoimmune pancreatitis, and salivary adenoid cystic carcinoma. Research on Calcb using gene knockdown models in these diseases has provided insights into its function and potential as a therapeutic target, helping to understand the disease mechanisms and develop new treatment strategies.

References:

1. Dallmayer, Marlene, Li, Jing, Ohmura, Shunya, Sannino, Giuseppina, Grünewald, Thomas G P. 2019. Targeting the CALCB/RAMP1 axis inhibits growth of Ewing sarcoma. In Cell death & disease, 10, 116. doi:10.1038/s41419-019-1372-0. https://pubmed.ncbi.nlm.nih.gov/30741933/

2. Gao, Feng, Liu, Guozhong, Wang, Jingwen, Zhang, Sheng, Liu, Qicai. 2021. Methylation of CALCA and CALCB in Pancreatic Ductal Adenocarcinoma. In Oxidative medicine and cellular longevity, 2021, 2088345. doi:10.1155/2021/2088345. https://pubmed.ncbi.nlm.nih.gov/34394823/

3. Liu, Qi-Cai, Chen, Falin, Wu, Chao-Yang, Zhao, Cheng-Fei, Lin, Xin-Hua. 2017. CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis. In Cell death & disease, 8, e2591. doi:10.1038/cddis.2017.32. https://pubmed.ncbi.nlm.nih.gov/28151472/

4. Dai, Chaobin, Zhang, Bin, Liao, Yunyang, Zeng, Kai, Zhu, Xiaofeng. 2021. CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland. In Disease markers, 2021, 5546858. doi:10.1155/2021/5546858. https://pubmed.ncbi.nlm.nih.gov/34234876/