Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.
Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.
Oncogene. 2022 Aug;41(33):3979-3990. doi: 10.1038/s41388-022-02386-8. Epub 2022 Jul 7.
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.
环状 RNA（circRNAs）在透明细胞肾细胞癌（ccRCC）中发挥着关键作用。然而，它们在舒尼替尼耐药中的作用在很大程度上尚不清楚。本研究鉴定了一种新型环状 RNA，命名为 circME1，其有助于 ccRCC 中舒尼替尼耐药的发展。circME1 还促进了 ccRCC 细胞的增殖、迁移和侵袭。进一步的机制分析表明，circME1 与 U1 snRNP 在其亲本基因 ME1 的启动子上相互作用，从而上调 ME1 的表达，增强 ccRCC 的有氧糖酵解，并促进其恶性表型。此外，ME1 特异性抑制剂可有效抑制 circME1 的致癌功能。总之，本研究表明 circME1/ME1 通路参与了 ccRCC 的进展和舒尼替尼耐药的发展，可能被用于癌症治疗。
