lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation

Changhong Liu; Zixuan Peng; Peiyao Li; Haijuan Fu; Jianbo Feng; Yan Zhang; Tao Liu; Yang Liu; Qing Liu; Qiang Liu; Di Li; Minghua Wu

doi:10.1016/j.omtn.2020.01.008

lncRNA RMST Suppressed GBM Cell Mitophagy through Enhancing FUS SUMOylation

Mol Ther Nucleic Acids. 2020 Mar 6:19:1198-1208. doi: 10.1016/j.omtn.2020.01.008. Epub 2020 Jan 18.

Authors

Changhong Liu¹, Zixuan Peng², Peiyao Li², Haijuan Fu², Jianbo Feng², Yan Zhang², Tao Liu², Yang Liu², Qing Liu³, Qiang Liu⁴, Di Li², Minghua Wu⁵

Affiliations

¹ Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China; Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, Shandong 250033, China.
² Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China.
³ The Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
⁴ The Third Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
⁵ Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China. Electronic address: wuminghua554@aliyun.com.

Abstract

Long non-coding RNAs (lncRNAs) play a significant role in post-translational modifications of proteins, yet the importance of lncRNAs for SUMOylation is unknown. rhabdomyosarcoma 2 associated transcript (RMST) expression in glioma tissues and normal brain tissues was measured by quantitative real-time PCR and in situ hybridization. The functional roles of RMST in astrocytomas were demonstrated by a series of in vitro experiments. The potential mechanisms of RMST for SUMOylation were investigated by RNA immunoprecipitation, RNA pull-down, western blotting, and coimmunoprecipitation assays. We first demonstrated the oncogenic activity of lncRNA RMST by inhibiting glioma cells mitophagy. We also first determined that RMST is an enhancer of FUS SUMOylation, especially boosting SUMO1 modification at K333. SUMOylation induced by RMST contributes to the interaction between FUS and heterogeneous nuclear ribonucleoprotein D (hnRNPD) and stabilized their expression and cells mitophagy. Importantly, lncRNA RMST could serve as a promising prognostic factor for glioma patients. Our results demonstrated a previously unknown function of lncRNAs worked as an enhancer in FUS SUMOylation, and RMST will be a significant guide for the development of medications targeting gliomas.

Keywords: GBM; SUMOylation; lncRNA; oncogene.