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RNF213 suppresses carcinogenesis in glioblastoma by affecting MAPK/JNK signaling pathway

Clinical and Translational Oncology volume 22, pages 1506–1516 (2020)Cite this article

Abstract

Purpose

Glioblastoma is the most common malignant brain tumor in central nervous system. Due to absence of the mechanism underlying glioblastoma, the clinical outcome is poor. RNF213 is a ring finger protein and mutation in RNF213 gene is detected in cancers. But the role of RNF213 in glioblastoma is unknown.

Methods

RNF213 expression was detected by qPCR, western blotting, IHC technology. RNF213 was overexpressed in plasmid pcDNA3.1. Assays including CCK-8, plate colony formation, wound healing, transwell and FITC/PI dye were used to detect cell behaviors.

Results

RNF213 was shown to express much lower in tumor tissues and in tumor cell lines compared to control. The patients with higher RNF213 expression displayed longer survival time. When RNF213 was overexpressed in U87MG cells, cell proliferation and colony formation were inhibited significantly. The ability of cell migration and invasion was also suppressed. FAC analysis demonstrated that cell apoptosis was increased after RNF213 overexpression. But cell cycle distribution was not affected by RNF213. Then the expression level of MEKK1, JNK, c-Jun, and cdc42 was decreased after RNF213 overexpression, but increased reversely when RNF213 was knocked down by RNAi technology.

Conclusions

RNF213 suppresses carcinogenesis and affects MAPK/JNK signaling pathway in glioblastoma. This study suggests that RNF213 might be a promising target for therapy of glioblastoma.

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Acknowledgement

This work was supported by National Natural Science Foundation of China (No.81760446 and No.81660420), Key Project of Jiangxi Natural Science Foundation (No.20171ACB20035), Construction Plan of the Superior Science and Technology Innovation Team of Jiangxi Province (No.20152BCB24009) and Foreign Science and Technology Cooperation Plan of Jiangxi Province (No.20151BDH8009).

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Author notes

  1. X. Wang and M. Ye contributed to this study equally.

Affiliations

  1. Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    X. Wang, M. Ye, M. Wu, H. Fang, B. Xiao, L. Xie & X. Zhu

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  1. X. Wang
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Correspondence to X. Zhu.

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Wang, X., Ye, M., Wu, M. et al. RNF213 suppresses carcinogenesis in glioblastoma by affecting MAPK/JNK signaling pathway. Clin Transl Oncol 22, 1506–1516 (2020). https://doi.org/10.1007/s12094-020-02286-x

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Keywords

  • RNF213
  • MAPK
  • JNK
  • Glioblastoma