HGF/c-Met Promote Renal Carcinoma Cancer Stem Cells Enrichment Through Upregulation of Cir-CCDC66

Increasing studies have suggested that circular RNAs play an important function in the process of numerous cancers. We aimed to investigate the possible role of cir-CCDC66 in renal carcinoma cancer. As cancer stem cells are responsible for the renal carcinoma cancer tumor growth and resistance to conventional therapy, we focus on the cir-CCDC66 influence on renal carcinoma cancer stem cells. In this study, we performed experiments in human renal tubular epithelial cell HK2 cells and several renal carcinoma cancer cancer cell lines. The results showed that cir-CCDC66 was upregulated not only in renal carcinoma cancer cancer cell lines but also in cancer stem cell spheres. What’s more, the results showed that cir-CCDC66 enhanced the cancer stem cell enrichment. Further mechanistic studies showed that hepatocyte growth factor/c-Met pathway was activated in cancer stem cell enrichment and responsible for the cir-CCDC66 upregulation. Inhibition of hepatocyte growth factor/c-Met could block cir-CCDC66-induced cancer stem cell enrichment. In conclusion, our research revealed a novel mechanism between hepatocyte growth factor/c-Met/cir-CCDC66 and cancer stem cell enrichment. We verified that cir-CCDC66 could be a promising biomarker and therapy target for renal carcinoma cancer treatment.