Regucalcin Functions in Cell Regulation and Cancer Biology

Regucalcin is a highly conserved calcium-binding protein that lacks classical EF-hand motifs but exerts pivotal roles in maintaining intracellular calcium homeostasis and modulating a wide array of signalling cascades. Originally identified as a liver-enriched factor involved in Ca2+ signalling, regucalcin regulates key enzymes including protein kinases, phosphatases and nitric oxide synthase, and governs nuclear processes such as DNA and RNA synthesis. In normal tissues, it contributes to cell survival by buffering cytosolic calcium and restraining apoptotic triggers, while in proliferating cells it exerts inhibitory control over cell cycle progression. Dysregulation of regucalcin expression is a hallmark of various cancers, where its downregulation correlates with enhanced tumour cell proliferation, invasion and poor patient prognosis. Conversely, forced overexpression of regucalcin in cancer models induces cell cycle arrest, suppresses oncogenic pathways such as Ras–MAPK and PI3K–Akt, upregulates tumour suppressors p53 and p21, and attenuates anti-apoptotic factors. Emerging evidence also implicates regucalcin in shaping the tumour immune microenvironment by influencing immune cell infiltration and cytokine networks. These multifaceted activities position regucalcin as a tumour suppressor and a prospective therapeutic target for restoring calcium-dependent regulatory networks in cancer therapy.

Research from Nature Portfolio

Recent studies have revealed that regucalcin expression in lung squamous cell carcinoma is significantly reduced compared with adjacent normal tissue, and that its level closely correlates with patient survival and clinical staging. Analyses of tumour samples demonstrated that low regucalcin expression associates with altered humoral and cellular immune responses, including shifts in plasma cells, macrophage subsets and T-cell populations. A novel competing endogenous RNA network involving regucalcin, specific microRNAs and long non-coding RNAs has been delineated, pointing to complex post-transcriptional regulation. High regucalcin expression predicts differential response to chemotherapy and immunotherapy, suggesting its utility as a prognostic biomarker and stratification factor for personalised treatment. Additional work in hepatocellular carcinoma has confirmed that diminished regucalcin levels in tumour lesions are linked to larger tumours, advanced TNM stage and lower overall survival. Epigenetic analyses indicate that promoter methylation contributes to its downregulation and that regucalcin-co-expressed gene modules modulate apoptotic and adhesion pathways, underscoring its clinical relevance as a prognostic indicator.

Regucalcin Functions in Cell Regulation and Cancer Biology publication trend

The graph below shows the total number of articles in regucalcin functions in cell regulation and cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Regucalcin: A calcium-binding regulatory protein that controls intracellular Ca2+ signalling and enzyme activities without EF-hand motifs.

ceRNA network: A regulatory circuit in which long non-coding RNAs, microRNAs and mRNAs compete for binding to shared microRNA response elements, influencing gene expression.

Tumour immune microenvironment: The complex network of immune cells, cytokines and stromal factors surrounding a tumour, which affects progression and therapy response.

DNA methylation: An epigenetic modification involving addition of methyl groups to cytosine residues, often leading to transcriptional silencing.

Cell cycle arrest: A regulatory mechanism that halts cell division at specific checkpoints (G1, S or G2/M) in response to internal or external cues.

References

1. Regucalcin Is a Potential Regulator in Human Cancer: Aiming to Expand into Cancer Therapy. Cancers (2023).
2. RGN as a prognostic biomarker with immune infiltration and ceRNA in lung squamous cell carcinoma. Scientific Reports (2023).
3. Prolonged survival in hepatocarcinoma patients with increased regucalcin gene expression: HepG2 cell proliferation is suppressed by overexpression of regucalcin in vitro. International Journal of Oncology (2016).
4. The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways. Apoptosis (2013).
5. Live and let die: epigenetic modifications of Survivin and Regucalcin in non-small cell lung cancer tissues contribute to malignancy. Clinical Epigenetics (2019).