CircME1 promotes aerobic glycolysis and sunitinib resistance of clear cell renal cell carcinoma through cis-regulation of ME1

CircME1 通过顺式调控 ME1 促进有氧糖酵解和透明细胞肾细胞癌的舒尼替尼耐药性

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作者:Ming-Xiao Zhang #, Jia-Li Wang #, Cheng-Qiang Mo #, Xiao-Peng Mao #, Zi-Hao Feng, Jia-Ying Li, Hai-Shan Lin, Hong-de Song, Quan-Hui Xu, Ying-Han Wang, Jun Lu, Jin-Huan Wei, Hui Han, Wei Chen, Hai-Ping Mao, Jun-Hang Luo, Zhen-Hua Chen

Abstract

Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.

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