CircPDK1 promotes RCC cell migration and invasion through the miR-377-3p/NOTCH1 axis

Abstract Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are widely expressed in various tissue types. Recent studies have indicated that circRNAs involved in multiple tumorigenesis processes, and the potential significance of circRNAs remains to be explored. However, the roles roles and underlying mechanisms of circRNAs in clear cell renal cell carcinoma (RCC) remain unclear. We found that CircPDK1 is highly expressed in RCC by circRNA-seq assay. Moreover, the functional enrichment experiments showed that CircPDK1 is significantly associated with RCC metastasis. Eighty pairs of clinical samples were analyzed, and the results showed a correlation between CircPDK1 and lymph node and distant organ metastases in RCC. RNA-sequencing following knockdown of CircPDK1 revealed significant changes in the expression of many molecules in the metastasis-associated pathway. After bioinformatics prediction, we verified the relationships between CircPDK1 and miR-377-3p and between miR-377-3p and NOTCH1 by a luciferase reporter assay. Furthermore, the effect of CircPDK1 on RCC metastasis can be functionally influenced by miR-377-3p and NOTCH1. Altogether, our study shows that the CircPDK1 - miR-377-3p - NOTCH1 axis plays an important role in RCC metastasis, suggests CircPDK1 might serve as a potential therapeutic target for RCC treatment.