Altered expression levels of IDH2 are involved in the development of colon cancer

Qiang Lv,Xiaofang Xu,Zhenxiao Li,Xichen Zhang,Wei Li,Xiaoxia Jin,Guocai Zhang,Le Chang,Ju Yang,Jianhua Li,Feng Gao,Pengtao Gong,Shenyang Xing

doi:10.3892/etm.2012.676

Abstract

IDH2 encodes a mitochondrial metabolic enzyme that converts isocitrate to α-ketoglutarate (α-KG) by reducing nicotinamide adenine dinucleotide phosphate (NADP+) to NADPH and participates in the citric acid cycle for energy production. Notably, this gene has been shown to be critical for cell proliferation. The abnormal expression of IDH2 has been reported in several types of cancer, and mutations in IDH2 have been identified in gliomas and acute myelogenous leukemia. The overexpression of IDH2 has been reported in endometrial, prostate and testicular cancer as well as in Kashin-Beck disease. In this study, we observed that IDH2 expression was significantly downregulated in early phase but was upregulated in advanced phase colon carcinoma compared to peritumoral tissues. In addition, we demonstrated that the growth of a colon carcinoma cell line was inhibited by IDH2-siRNA and increased following transfection with an IDH2-overexpressing plasmid. These results indicate that IDH2 may play a unique role in the development of colon carcinoma.

Highlights

Colorectal cancer (CRC) is one of the most common malignances in the world and ranks as the fifth most common cancer type and the fourth most common cause of cancerrelated mortalities in China [1]
The expression of IDH2 mRNA in HCT-8 cells transfected with IDH2 siRNA or the overexpression plasmid was detected by quantitative real‐time RT-PCR
To investigate whether the expression level of the IDH2 gene contributes to colon cancer development, the repression and overexpression of IDH2 was examined in HCT-8 cells using the MTT assay to assess the effects on cell growth

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignances in the world and ranks as the fifth most common cancer type and the fourth most common cause of cancerrelated mortalities in China [1]. The incidence of CRC has increased rapidly in recent years, in economically developed coastal cities [2,3]. Previous studies have greatly improved our understanding of the mechanisms of CRC, the etiology and pathogenesis remain unclear. These mutations may predispose cells to neoplasia either by activating oncogenes or inactivating tumor-suppressor genes

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