Circular RNA hsa-circ-0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression

Abstract

Background: FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa-circ-0068871 is a circRNA generated from several exons of FGFR3. However, the potential functional role of hsa-circ-0068871 in BCa remains largely unknown. Here we aim to evaluate the role of hsa-circ-0068871 in BCa. Methods: We selected miR-181a-5p as the potential target miRNA of hsa-circ-0068871. The expression levels of hsa-circ-0068871 and miR-181a-5p were examined in BCa tissues and paired adjacent normal tissues by quantitative real-time PCR. To characterize the function of hsa-circ-0068871, BCa cell lines were stably infected with lentivirus targeting hsa-circ-0068871, followed by examinations of cell proliferation, migration and apoptosis. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa-circ-0068871 in BCa. Biotinylated RNA probe pull-down assay, fluorescence in situ hybridization and luciferase reporter assay were conducted to confirm the relationship between hsa-circ-0068871, miR-181a-5p and FGFR3. Results: Hsa-circ-0068871 is over-expressed in BCa tissues and cell lines, whereas miR-181a-5p expression is repressed. Depletion of has-circ-0068871 or upregulation of miR-181a-5p inhibited the proliferation and migration of BCa cells in vitro and in vivo. Mechanistically, hsa-circ-0068871 upregulated FGFR3 expression and activated STAT3 by targeting miR-181a-5p to promote BCa progression. Conclusions: Hsa-circ-0068871 regulates the miR-181a-5p/FGFR3 axis and activates STAT3 to promote BCa progression, and it may serve as a potential biomarker.