Prolonged survival in hepatocarcinoma patients with increased regucalcin gene expression: HepG2 cell proliferation is suppressed by overexpression of regucalcin in vitro

Yamaguchi,Masayoshi; Osuka,Satoru; Weitzmann,M.  Neale; El-Rayes,Bassel   F.; Shoji,Mamoru; Murata,Tomiyasu

doi:10.3892/ijo.2016.3669

Prolonged survival in hepatocarcinoma patients with increased regucalcin gene expression: HepG2 cell proliferation is suppressed by overexpression of regucalcin in vitro

Authors:
- Masayoshi Yamaguchi
- Satoru Osuka
- M. Neale Weitzmann
- Bassel F. El-Rayes
- Mamoru Shoji
- Tomiyasu Murata
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Affiliations: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA, Department of Neurosurgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA, The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30322, USA, Laboratory of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468-8503, Japan
Published online on: August 23, 2016 https://doi.org/10.3892/ijo.2016.3669
Pages: 1686-1694

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and ranks third in overall global cancer-related mortality rates. Importantly, in this study gene expression data demonstrate that prolonged survival in HCC patients is associated with increased regucalcin gene expression. Regucalcin has been shown to play a pivotal role as a transcription repressor and diminished expression or activity of regucalcin may play a key role in the development of human carcinogenesis. Indeed, overexpression of regucalcin suppressed the proliferation, cell death, and migration of human HCC HepG2 cells in vitro. Mechanistically, regucalcin induced G1 and G2/M phase cell cycle arrest of HepG2 cells through suppression of multiple signaling pathways including Ras, Akt, MAP kinase and SAPK/JNK and by increasing the tumor suppressors p53 and Rb. Furthermore, the oncogenes c-fos and c-myc were suppressed by overexpression of regucalcin, and overexpression of regucalcin caused an increase in p21 and a decrease in NF-κB p65 and β-catenin. These findings suggest that regucalcin may play a potential role as a suppressor of human HCC, and that diminished expression of regucalcin may predispose patients to development of HCC. Overexpression of regucalcin may constitute a novel therapeutic approach to treating HCC.

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