Hsa_circ_0041103 induces proliferation, migration and invasion in bladder cancer via the miR-107/FOXK1 axis

Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1282-1290. doi: 10.26355/eurrev_202102_24832.

Abstract

Objective: CircRNAs have been proven to be vital during the process of malignant tumors. Their functions in bladder cancer (BCa) process remain largely unclear. This study aims to elucidate the role of circ0041103 in affecting the malignant phenotypes of BCa, and the possible molecular mechanism.

Patients and methods: Circ0041103 expression levels in BCa tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The clinical significance of circ0041103 in influencing tumor size, tumor staging and lymphatic metastasis of BCa was analyzed. Regulatory effects of circ0041103 on proliferative and metastatic capacities of T24 and UM-UC-3 cells were examined through functional experiments. The binding target of circ0041103 and its downstream protein were predicted by online bioinformatic tools, which were further confirmed by Dual-Luciferase reporter assay and Pearson correlation test. The role of circ0041103/miR-107/ FOXK1 axis in regulating BCa process was explored by rescue experiments.

Results: Circ0041103 was abnormally upregulated in BCa tissues and cell lines. Its level was higher in BCa tissues with a larger tumor size, or worse tumor staging, or BCa cases with lymphatic metastasis. Knockdown of circ0041103 inhibited proliferative and metastatic capacities of T24 and UM-UC-3 cells. MiR-107 was the binding target of circ0041103, and FOXK1 was the downstream gene of miR-107. Overexpression of circ0041103 could reverse the inhibited proliferative and metastatic capacities of T24 and UM-UC-3 cells overexpressing miR-107.

Conclusions: Circ0041103 is upregulated in BCa and predicts a poor prognosis in BCa. It stimulates BCa cells to proliferate and migrate via the miR-107/FOXK1 axis.

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • FOXK1 protein, human
  • Forkhead Transcription Factors
  • MIRN107 microRNA, human
  • MicroRNAs
  • RNA, Circular