Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2.
Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2.
复制标题
环状RNA circRNF13通过SUMO2抑制鼻咽癌增殖和转移
DOI：
10.1186/s12943-021-01409-4
复制
发表时间：
2021-08-31
期刊：
影响因子：
37.3
通讯作者：
Xiong W
中科院分区：
文献类型：
--
作者：
Mo Y;Wang Y;Zhang S;Xiong F;Yan Q;Jiang X;Deng X;Wang Y;Fan C;Tang L;Zhang S;Gong Z;Wang F;Liao Q;Guo C;Li Y;Li X;Li G;Zeng Z;Xiong W
Background
Circular 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).
Methods
We 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.
Results
We 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.
Conclusions
Our 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.
登录
查看更多内容
影响因子：
9.7
作者：
Fan, Chunmei;Qu, Hongke;Zeng, Zhaoyang
通讯作者：
Zeng, Zhaoyang
circMAN1A2可以作为恶性肿瘤的新型血清生物标志物
影响因子：
5.7
作者：
Fan, Chun-Mei;Wang, Jin-Peng;Zeng, Zhao-Yang
通讯作者：
Zeng, Zhao-Yang
影响因子：
11.2
作者：
Kong, Ling-Min;Liao, Cheng-Gong;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan
人类癌症中的环状RNA
影响因子：
37.3
作者：
Wang Y;Mo Y;Gong Z;Yang X;Yang M;Zhang S;Xiong F;Xiang B;Zhou M;Liao Q;Zhang W;Li X;Li X;Li Y;Li G;Zeng Z;Xiong W
通讯作者：
Xiong W
影响因子：
8
作者：
Tang, Le;Xiong, Wei;Zeng, Zhaoyang
通讯作者：
Zeng, Zhaoyang