circ_001504 promotes the development of renal cell carcinoma by sponging microRNA-149 to increase NUCB2

Rui Xin  ^{1   2} , Danhua Qu  ^{1   3} , Huiying Xu  ^{1   4} , Dawei Chen  ^{5   6} Affiliations

• PMID: 33110207
• DOI: 10.1038/s41417-020-00247-8

Abstract

Renal cell carcinoma (RCC) accounts for over 90% of primary renal tumors in adults. Although treatment approaches have steadily improved over the years, the prognosis outcome remains poor. With the aim of developing novel targets for RCC treatment, we explored the role of the circular RNA (circRNA) circ_001504 in the progression of RCC. We initially detected the expression of circ_001504 and microRNA (miRNA)-149 in RCC tissues and cells. RT-qPCR results showed that circ_001504 was highly expressed in RCC tissues, whereas miR-149 was poorly expressed. Interestingly, downregulation of circ_001504 suppressed malignant phenotypes in RCC cells, and upregulation of miR-149 exerted a similar effect. Bioinformatics analysis suggested potential binding sites between circ_001504 and miR-149, verified by a dual-luciferase reporter gene assay. Next, we identified nucleobindin 2 (NUCB2), a calcium-binding protein, as a target gene of miR-149. Furthermore, our data suggested that circ_001504 might serve as a competing endogenous RNA of miR-149, serving to elevate the expression of NUCB2. The silencing of circ_001504 resulted in decreased NUCB2 expression, which could be reversed by miR-149 inhibition. In addition, in vivo experiments demonstrated that circ_001504 depletion could suppress tumor growth in an established mouse RCC model. Collectively, reduced expression of circ_001504 lowered NUCB2 expression by sponging miR-149, thereby attenuating RCC progression, providing insight into circ_001504/miR-149/NUCB2 feedback loop into RCC treatment.