CircME1 promotes aerobic glycolysis and sunitinib resistance of clear cell renal cell carcinoma through cis-regulation of ME1
Ming-xiao Zhang, Jiali Wang, Chengqiang Mo, Xiaopeng Mao, Zihao Feng, Jiaying Li, Haishan Lin, Hongde Song, Quanhui Xu, Yinghan Wang, Jun Lü, Jinhuan Wei, Hui Han, Wei Chen, Haiping Mao, Junhang Luo, Zhenhua 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.