Regucalcin downregulation in human cancer

Regucalcin is a unique calcium-binding protein first discovered in rat liver in 1978. Regucalcin has multiple functions as an inhibitor of various cellular signaling pathways that regulate cell activity. The expression of the regucalcin gene can be altered by various physiological and pathological factors such as diet (nutrients), hormones, diabetes, alcohol and drugs. Several transcription factors have been identified on the regucalcin gene, including AP-1, NF1-A1, RGPR-p117, β-catenin, NF-κB, STAT3 and hypoxia-inducible factor-1α (HIF-1α). Notably, regucalcin plays an important role in the development of several cancers by controlling cell growth. Clinically, many studies have reported that the expression of the regucalcin gene is downregulated in various human cancers. In addition, higher expression of regucalcin in tumor tissue has been associated with longer patient survival, suggesting that regucalcin may act as a potential suppressor of various types of human cancer. Regucalcin may offer a novel therapeutic strategy and diagnostic tool for cancer treatment. However, the underlying mechanism by which regucalcin expression is reduced in human cancer is still unclear. A deeper understanding of regucalcin reduction and function in cancer is needed to discover potential resistance mechanisms and biomarkers, and to improve regucalcin-targeting agents. We review recent findings on regucalcin gene expression in cancer. We discuss the possible mechanisms by which regucalcin expression is downregulated in cancer cells to facilitate understanding of how regucalcin regulates cell growth function. This mini-review may lead to better therapeutic targets with regucalcin.