Regucalcin as a new tumor suppressor gene?

The research team of the Health Sciences Research Centre of the University of Beira Interior (CICS-UBI) led by Sílvia Socorro, together with other international researchers, has been publishing several studies aiming at clarifying the role of the calcium-binding protein Regucalcin (RGN) in the regulation of physiology (and pathophysiology) of various tissues and organs. Recently, the CICS-UBI group have published a review article in the journal “Current molecular medicine”, which makes an exhaustive analysis of all published studies related to the expression and function of this protein, and its association with tumorigenesis. Different types of neoplastic tissues are characterized by presenting loss of RGN expression comparatively with non-neoplastic tissues, and this decrease is also correlated with the differentiation and aggressiveness of tumors. Interestingly, a panoply of hormonal and non-hormonal factors, determinant for tissue homeostasis, seem to regulate the expression levels of RGN. In addition, this review evidenced the properties of RGN as a multifunctional protein, being involved in the regulation of fundamental biological processes, such as cell proliferation and cell death, metabolism, and oxidative stress, all recognized as hallmarks of cancer. RGN also acts counteracting age-related deterioration of cell functions and, RGN overexpression showed to suppress the development of tumors in animal models. Therefore, the gathered data pointed RGN as tumor suppressor gene, at the same time that stimulated the development of research strategies to manipulate the RGN tissue expression levels, which could be viewed as a possibility to prevent the development and progression of cancer.

Authors and Affiliations:

Vaz CV, Correia S, Cardoso HJ, Figueira MI, Marques R, Maia CJ, Socorro S

CICS-UBI, Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.

Abstract:

Regucalcin (RGN) is a multifunctional protein that was first described as a calcium (Ca²⁺)-binding protein playing a relevant role in the maintenance of intracellular Ca2+ concentration. However, due to its downregulated expression with aging, RGN is also known as senescence marker protein-30. The RGN protein is an X-chromosome gene product, whose transcription is regulated by a myriad of hormonal and non-hormonal factors. Besides the well-known role in Ca²⁺ homeostasis, RGN has also been linked to the control of several intracellular signaling pathways, and basic biological processes, such as oxidative stress, cell proliferation, apoptosis, and metabolism. RGN has been shown to have antioxidant properties by its activity reducing the production of reactive oxygen species and increasing the antioxidant defenses. The role of RGN suppressing cell proliferation is associated with the regulation of expression of oncogenes and tumor suppressor genes. It results clear that all the existent knowledge implicates RGN in the control of the main biological processes actually recognized as the hallmarks of cancer. Moreover, it has been shown that tumor onset and progression are underpinned by the loss of RGN expression, whereas RGN overexpression showed to have a protective role against the development of chemically-induced tumors. This review describes the mechanisms that control the tissue expression of RGN and discusses the experimental evidence that indicate RGN as a new tumor suppressor protein.

Journal: Current Molecular Medicine

Link: http://benthamscience.com/journals/current-molecular-medicine/article/143971/