Hsa_circ_0001361 promotes bladder cancer invasion and metastasis through miR-491-5p/MMP9 axis.

Abstract

Circular RNAs (circRNAs) have been increasingly indicated to be important participants in the development and progression of various malignant tumors. Our previous studies found that hundreds of circRNAs were aberrantly expressed in bladder cancer (BC) by high-throughput sequencing and we have confirmed that the downregulated circRNAs circHIPK3, circRNA BCRC-3, and circNR3C1 played inhibitory roles in BC progression. In this study, we focused on the upregulated circRNAs and identified a novel circular RNA, hsa_circ_0001361 (circ0001361), was expressed at high levels in BC tissues and cell lines based on RNA-Seq data and qRT-PCR analysis, and it was positively corelated with pathologic grade and muscle invasion. Moreover, Kaplan-Meier survival analysis implied that BC patients with high circ0001361 expression level had a poor overall survival. Functionally, circ0001361 promoted BC cell invasion and metastasis both in vitro and in vivo, but had no effect on cell cycle and proliferation. Mechanistically, RNA sequencing analysis indicated that MMP9 was upregulated in circ0001361-overexpressed BC cells, and MMP9 was verified to mediate circ0001361-induced cell migration and invasion. Furthermore, we demonstrated that circ0001361 could directly interact with miR-491-5p to upregulate MMP9 expression. Collectively, our findings indicate that circ0001361 plays oncogenic role in BC invasion and metastasis through targeting the miR-491-5p/MMP9 axis, and it might be a potential novel target for BC therapy.