Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

Abstract

Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumorsuppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines.However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstratedthat NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpressionof NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From ourresearch, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression ofNDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 andp27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits theproliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insightsinto the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effectivecandidate for the treatment of children with neuroblastoma.

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