Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro

• Published in: International journal of oncology Vol. 54; no. 1; pp. 188 - 198
• Main Authors: Yamaguchi, Masayoshi, Osuka, Satoru, Hankinson, Oliver, Murata, Tomiyasu
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.01.2019; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Breast cancer; Calcium binding proteins; Calcium-Binding Proteins - genetics; Cancer genetics; Cancer research; Carcinoma, Renal Cell - genetics; Cell cycle; Cell Cycle Checkpoints; Cell death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal cancer; Deoxyribonucleic acid; DNA; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Growth factors; Health aspects; Homeostasis; Human subjects; Humans; Hypertension; In Vitro Techniques; Intracellular Signaling Peptides and Proteins - genetics; Kidney cancer; Kidney Neoplasms - genetics; Kinases; Liver cancer; Medical prognosis; Pancreatic cancer; Patient outcomes; Physiological aspects; Proteins; Renal cell carcinoma; RNA polymerase; Rodents; Signal Transduction; Survival Analysis; Transcription factors; Tumor necrosis factor-TNF; Up-Regulation; United States > US
• DOI: 10.3892/ijo.2018.4611
• ISSN: 1019-6439

Renal cell carcinoma (RCC), which is a type of cancer found in the kidney tubule, is among the 10 most frequently occurring human cancers. Regucalcin plays a potential role as a regulator of transcriptional activity, and its downregulated expression or activity may contribute to the promotion of human cancers. In this study, we investigated the involvement of regucalcin in human RCC. Regucalcin expression was compared in 23 normal and 29 tumor samples of kidney cortex tissues of patients with clear cell RCC obtained through the Gene Expression Omnibus (GEO) database (GSE36895). Regucalcin expression was downregulated in the tumor tissues. The prolonged survival of patients with clear cell RCC was demonstrated to be associated with a higher regucalcin gene expression in the TCGA dataset. The overexpression of regucalcin suppressed the colony formation, proliferation and the death of human clear cell RCC A498 cells in vitro. Mechanistically, the overexpression of regucalcin induced the G1 and G2/M phase cell cycle arrest of A498 cells through the suppression of multiple signaling components, including Ras, PI3 kinase, Akt and mitogen‑activated protein (MAP) kinase. Importantly, the overexpression of regucalcin led to an elevation in the levels of the tumor suppressors, p53, Rb and the cell cycle inhibitor, p21. The levels of the transcription factors, c‑fos, c‑jun, nuclear factor‑κB p65, β‑catenin and signal transducer and activator of transcription 3, were suppressed by regucalcin overexpression. On the whole, the findings of this study suggest that regucalcin plays a suppressive role in the promotion of human RCC. The overexpression of regucalcin by gene delivery systems may thus prove to be a novel therapeutic strategy for RCC.