Regucalcin Is a Potential Regulator in Human Cancer: Aiming to Expand into Cancer Therapy

SIMPLE SUMMARY: Regucalcin plays a multifunctional role in the regulation of cell function and expresses a repressive effect in the growth of normal cells. Of note, there is increasing evidence that regucalcin plays a potential role as a suppressor in several types of human cancer. Regucalcin expression is downregulated in the tumor tissues of cancer patients. Patients with higher levels of regucalcin in tumor tissues have shown longer survival. Overexpressed regucalcin suppresses the development of carcinogenesis. Extracellular regucalcin has been shown to suppress the proliferation of cancer cells. Delivery of the regucalcin gene may offer novel therapeutic benefits. This review discusses the potential role of regucalcin in the suppression of human cancer. ABSTRACT: Regucalcin, a calcium-binding protein lacking the EF-hand motif, was initially discovered in 1978. Its name is indicative of its function in calcium signaling regulation. The rgn gene encodes for regucalcin and is situated on the X chromosome in both humans and vertebrates. Regucalcin regulates pivotal enzymes involved in signal transduction and has an inhibitory function, which includes protein kinases, protein phosphatases, cysteinyl protease, nitric oxide dynthetase, aminoacyl-transfer ribonucleic acid (tRNA) synthetase, and protein synthesis. This cytoplasmic protein is transported to the nucleus where it regulates deoxyribonucleic acid and RNA synthesis as well as gene expression. Overexpression of regucalcin inhibits proliferation in both normal and cancer cells in vitro, independent of apoptosis. During liver regeneration in vivo, endogenous regucalcin suppresses cell growth when overexpressed. Regucalcin mRNA and protein expressions are significantly downregulated in tumor tissues of patients with various types of cancers. Patients exhibiting upregulated regucalcin in tumor tissue have shown prolonged survival. The decrease of regucalcin expression is linked to the advancement of cancer. Overexpression of regucalcin carries the potential for preventing and treating carcinogenesis. Additionally, extracellular regucalcin has displayed control over various types of human cancer cells. Regucalcin may hold a prominent role as a regulatory factor in cancer development. Supplying the regucalcin gene could prove to be a valuable asset in cancer treatment. The therapeutic value of regucalcin suggests its potential significance in treating cancer patients. This review delves into the most recent research on the regulatory role of regucalcin in human cancer development, providing a novel approach for treatment.