RRM2 is a potential prognostic biomarker with functional significance in glioma

Sun, Hongzhi; Yang, Bingya; Zhang, Hao; Song, Jingwei; Zhang, Yenan; Xing, Jicheng; Yang, Zhihui; Wei, Changyong; Xu, Tuoye; Yu, Zhennan; Xu, Zhipeng; Hou, Min; Ji, Minjun; Zhang, Yansong

doi:10.7150/ijbs.30114

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Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

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

Research Paper

RRM2 is a potential prognostic biomarker with functional significance in glioma

Hongzhi Sun^1,#, Bingya Yang^1,2,#, Hao Zhang^1,#, Jingwei Song¹, Yenan Zhang¹, Jicheng Xing³, Zhihui Yang³, Changyong Wei⁴, Tuoye Xu⁵, Zhennan Yu⁵, Zhipeng Xu^1,2, Min Hou¹, Minjun Ji^1,2✉, 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.

Citation:

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. https://www.ijbs.com/v15p0533.htm

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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

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APA

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. (2019). RRM2 is a potential prognostic biomarker with functional significance in glioma. International Journal of Biological Sciences, 15(3), 533-543. https://doi.org/10.7150/ijbs.30114.

ACS

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.

NLM

CSE

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. 2019. RRM2 is a potential prognostic biomarker with functional significance in glioma. Int J Biol Sci. 15(3):533-543.

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