Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2
| Autor: | Xianjie Jiang, Can Guo, Guiyuan Li, Yian Wang, Zhaojian Gong, Shanshan Zhang, Fuyan Wang, Yongzhen Mo, Zhaoyang Zeng, Wei Xiong, Yong Li, Qijia Yan, Le Tang, Qianjin Liao, Chunmei Fan, Shuai Zhang, Yumin Wang, Fang Xiong, Xiaoling Li, Xiangying Deng |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Ubiquitin-Protein Ligases Cell Proliferation Biology Models Biological Metastasis Mice Cell Movement Genes Reporter Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis 3' Untranslated Regions RC254-282 In Situ Hybridization Fluorescence Cell Proliferation Messenger RNA Glucose Transporter Type 1 SUMO2 Nasopharyngeal Carcinoma Cell growth Research Ubiquitination RNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell migration RNA Circular medicine.disease Molecular biology Xenograft Model Antitumor Assays circRNF13 Blot Reverse transcription polymerase chain reaction Gene Expression Regulation Neoplastic Disease Models Animal medicine.anatomical_structure Oncology Nasopharyngeal carcinoma Small Ubiquitin-Related Modifier Proteins Molecular Medicine Female RNA Interference Glycolysis GLUT1 |
| Zdroj: | Molecular Cancer Molecular Cancer, Vol 20, Iss 1, Pp 1-21 (2021) |
| ISSN: | 1476-4598 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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