UHRF2 mRNA Expression is Low in Malignant Glioma but Silencing Inhibits the Growth of U251 Glioma Cells in vitro

Ting-Feng Wu,Zuo-Peng Su,Bin Li,San-Song Chen,You-Xin Zhou,Ting Sun,Xue-Shun Xie,Wei Zhang,Gui-Lin Chen,Yong-Xin Wei,Zi-Wei Du

doi:10.7314/apjcp.2012.13.10.5137

Abstract

UHRF2 is a member of the ubiquitin plant homeo domain RING finger family, which has been proven to be frequently up-regulated in colorectal cancer cells and play a role as an oncogene in breast cancer cells. However, the role of UHRF2 in glioma cells remains unclear. In this study, we performed real-time quantitative PCR on 32 pathologically confirmed glioma samples (grade I, 4 cases; grade II, 11 cases; grade III, 10 cases; and grade IV, 7 cases; according to the 2007 WHO classification system) and four glioma cell lines (A172, U251, U373, and U87). The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines. An in vitro assay was performed to investigate the functions of UHRF2. Using a lentivirus-based RNA interference (RNAi) approach, we down-regulated UHRF2 expression in the U251 glioma cell line. This down- regulation led to the inhibition of cell proliferation, an increase in cell apoptosis, and a change of cell cycle distribution, in which S stage cells decreased and G2/M stage cells increased. Our results suggest that UHRF2 may be closely related to tumorigenesis and the development of gliomas.

Highlights

Malignant glioma, especially glioblastoma multiforme, is the most frequent primary brain tumor and the most malignant neoplasm, with predominant astrocytic differentiation (Louis et al, 2007)
The expression of UHRF2 mRNA was significantly lower in the grade III and grade IV groups compared with the noncancerous brain tissue group, whereas its expression was high in A172, U251, and U373 glioma cell lines
It has been reported that the frequency of deletion at 9p23–p24 is highest in 73 tumor types (Knuutila et al, 1999)

Summary

Introduction

Especially glioblastoma multiforme, is the most frequent primary brain tumor and the most malignant neoplasm, with predominant astrocytic differentiation (Louis et al, 2007). Studies on UHRF2 have demonstrated that it constitutes a nodal point in the cell cycle network (Mori et al, 2011). Because this protein possesses a ubiquitin-like (UBL) domain, tandem Tudor domain (TTD), plant homeo domain (PHD) finger domain, SET and RING-associated (SRA) domain, and new gene (RING) finger domain at the C-terminus, its functions are more complex than an ordinary cell cycle hub protein (Glaab et al, 2010; Mori et al, 2012). The UHRF2 gene has been mapped to chromosome 9p24, in which many studies have proposed the presence of multiple tumor-associated genes (Kocarnik et al, 2010)

Methods

Results

Conclusion