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Int J Biol Sci 2019; 15(3):533-543. doi:10.7150/ijbs.30114

Research Paper

RRM2 is a potential prognostic biomarker with functional significance in glioma

Hongzhi Sun1,#, Bingya Yang1,2,#, Hao Zhang1,#, Jingwei Song1, Yenan Zhang1, Jicheng Xing3, Zhihui Yang3, Changyong Wei4, Tuoye Xu5, Zhennan Yu5, Zhipeng Xu1,2, Min Hou1, Minjun Ji1,2✉, Yansong Zhang5

1. Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
2. Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, 211166, China.
3. Department of Clinical laboratory, Bayi Hospital Affiliated to Nanjing University Of Chinese Medicine, Nanjing, Jiangsu, 210002, China.
4. Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
5. Department of Neurosurgery, Brain Hospital, affiliated to Nanjing medical University, Nanjing, 210029, China.
# Contributed equally.

Abstract

Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

Keywords: RRM2, Knock-down, G2/M phase arrest, ERK1/2, AKT

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Sun H, Yang B, Zhang H, Song J, Zhang Y, Xing J, Yang Z, Wei C, Xu T, Yu Z, Xu Z, Hou M, Ji M, Zhang Y. RRM2 is a potential prognostic biomarker with functional significance in glioma. Int J Biol Sci 2019; 15(3):533-543. doi:10.7150/ijbs.30114. Available from http://www.ijbs.com/v15p0533.htm