CircITGA7 regulates malignant phenotypes in bladder cancer cells via targeting miR-330-3p/KLF10 axis

Kaohsiung J Med Sci. 2024 Apr;40(4):324-334. doi: 10.1002/kjm2.12821. Epub 2024 Mar 25.

Abstract

Bladder cancer (BCa) is one of the common malignancies. Circular RNAs (circRNAs) play regulatory roles in cancer progression. CircITGA7 is a circRNA generated from several exons of ITGA7. The potential role of circITGA7 in BCa remains unknown and needs to be explored. Quantitative real time polymerase chain reaction (qRT-PCR) was used to assess circITGA7 and miR-330-3p expression in BCa tissues and cell lines. Kaplan-Meier analysis was used to evaluate the overall survival of these BCa patients. The biological function of circITGA7 was examined by overexpression of circITGA7 using CCK-8, EdU, wound-healing, and Transwell assays. Xenograft assay was performed to further validate the in vitro results. To explore the mechanism of circITGA7, luciferase reporter, RNA pull-down, fluorescence in situ hybridization (FISH) assays were employed to examine the binding interaction among circITGA7, miR-330-3p and kruppel-like factor 10 (KLF10). Western blot was used to study the protein levels of KLF10.CircITGA7 was downregulated in BCa tissues and cell lines and indicated longer overall survival. Moreover, circITGA7 restricted cell proliferation, migration and invasion of BCa through negatively regulating miR-330-3p. The in vivo model showed that circITGA7 influenced the tumor growth. Besides, the overexpression of miR-330-3p promoted cell progression by directly targeting KLF10. Mechanistically, circITGA7 inhibited BCa progression by activating KLF10 via targeting miR-330-3p.CircITGA7 alleviates BCa cell progression via circITGA7/hsa-miR-330-3p/KLF10 axis, which may provide novel therapeutic targets for BCa.

Keywords: KLF10; bladder cancer; circITGA7; miRNA sponge; miR‐330‐3p.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Early Growth Response Transcription Factors / genetics
  • Early Growth Response Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kruppel-Like Transcription Factors / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Phenotype
  • RNA, Circular / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Early Growth Response Transcription Factors
  • KLF10 protein, human
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • MIRN330 microRNA, human
  • RNA, Circular
  • integrin alpha7