Abstract

BackgroundFGFR3 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.MethodsWe 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.ResultsHsa_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.ConclusionsHsa_circ_0068871 regulates the miR-181a-5p/FGFR3 axis and activates STAT3 to promote BCa progression, and it may serve as a potential biomarker.

Highlights

  • Fibroblast growth factor receptor 3 (FGFR3) plays an important role in the development of bladder cancer (BCa)

  • FGFR3 is a carcinogenic driver in BCa, its mutation, activation and overexpression are related to the occurrence, development and invasion of BCa [11, 12]

  • The results showed that among the 12 patients, 1 patient (8.3%) had a mutation in FGFR3 (c.1138G > A) (Additional file 3), and 8 patients (66.7%) showed elevated FGFR3 expression

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Summary

Introduction

FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa_circ_0068871 is a circRNA generated from several exons of FGFR3. The potential functional role of hsa_circ_0068871 in BCa remains largely unknown. Various physiological functions of circRNAs have been discovered; for example, they serve as miRNA sponges to prevent mRNA translation, bind to RNA-associated proteins and influence gene expression by regulating splicing or transcription [17, 19], thereby playing key roles in biological processes and the progression of many diseases [20, 21]. How circRNA regulates FGFR3 and how this signalling axis may play a role in promoting BCa remain unclear

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