Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2

Molecular Cancer

Yong Li¹  Zhaojian Gong²  Qijia Yan³  Shuai Zhang³  Shanshan Zhang⁴  Fang Xiong⁴  Fuyan Wang⁵  Can Guo⁵  Yumin Wang⁶  Qianjin Liao⁷  Xiangying Deng⁸  Zhaoyang Zeng⁸  Xiaoling Li⁸  Yongzhen Mo⁸  Chunmei Fan⁸  Wei Xiong⁸  Guiyuan Li⁸  Yian Wang⁸  Le Tang⁸  Xianjie Jiang⁸ 

[1] Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA;Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, 410011, Changsha, Hunan, China;Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China;Department of Stomatology, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China;Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, 410078, Changsha, Hunan, China;Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, 410078, Changsha, Hunan, China;Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China;NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410078, Changsha, Hunan, China;NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410078, Changsha, Hunan, China;Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, 410078, Changsha, Hunan, China;

关键词: Nasopharyngeal carcinoma;    circRNF13;    SUMO2;    GLUT1;    Glycolysis;    Proliferation;    Metastasis;   

DOI  :  10.1186/s12943-021-01409-4

来源: Springer

【 摘 要 】

BackgroundCircular RNAs (circRNAs) are widely expressed in human cells and are closely associated with cancer development. However, they have rarely been investigated in the context of nasopharyngeal carcinoma (NPC).MethodsWe screened a new circRNA, circRNF13, in NPC cells using next-generation sequencing of mRNA. Reverse transcription polymerase chain reaction and RNA fluorescence in situ hybridization were used to detect circRNF13 expression in 12 non-tumor nasopharyngeal epithelial (NPE) tissues and 36 NPC samples. Cell proliferation was detected using MTT and flow cytometry assays, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. Cell glycolysis was analyzed using the Seahorse glycolytic stress test. Glucose transporter type 1 (GLUT1) ubiquitination and SUMOylation modifications were analyzed using co-immunoprecipitation and western blotting. CircRNF13 and Small Ubiquitin-like Modifier 2 (SUMO2) interactions were analyzed using RNA pull-down and luciferase reporter assays. Finally, to test whether circRNF13 inhibited NPC proliferation and metastasis in vivo, we used a xenograft nude mouse model generated by means of subcutaneous or tail vein injection.ResultsWe found that circRNF13 was stably expressed at low levels in NPC clinical tissues and NPC cells. In vitro and in vivo experiments showed that circRNF13 inhibited NPC proliferation and metastasis. Moreover, circRNF13 activated the SUMO2 protein by binding to the 3′- Untranslated Region (3′-UTR) of the SUMO2 gene and prolonging the half-life of SUMO2 mRNA. Upregulation of SUMO2 promotes GLUT1 degradation through SUMOylation and ubiquitination of GLUT1, which regulates the AMPK-mTOR pathway by inhibiting glycolysis, ultimately resulting in the proliferation and metastasis of NPC.ConclusionsOur results revealed that a novel circRNF13 plays an important role in the development of NPC through the circRNF13-SUMO2-GLUT1 axis. This study implies that circRNF13 mediates glycolysis in NPC by binding to SUMO2 and provides an important theoretical basis for further elucidating the pathogenesis of NPC and targeted therapy.

【 授权许可】

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