Circ_0084188 promotes colorectal cancer progression by sponging miR-654-3p and regulating kruppel-like factor 12

Kaohsiung J Med Sci. 2023 Nov;39(11):1062-1076. doi: 10.1002/kjm2.12749. Epub 2023 Sep 12.

Abstract

To investigate the biological role and mechanism of circ_0084188 in colorectal cancer (CRC). Real-time quantitative polymerase chain reaction and western blot assay were used to detect RNA levels and protein levels in CRC cell lines (HCT116 and SW480), respectively. Cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and colony formation assays. Cell apoptosis was determined using flow cytometry. Cell migration and invasion were measured by transwell assay. Sphere formation efficiency was determined by sphere formation assay. The interaction between microRNA-654-3p (miR-654-3p) and circ_0084188 or Kruppel-like factor 12 (KLF12) was confirmed by a dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Xenograft in CRC mice model was utilized for exploring the role of circ_0084188 in vivo.Circ_0084188 was overexpressed in CRC tissues and cells. Circ_0084188 silencing suppressed cell proliferation, migration, invasion, and stemness and induced apoptosis in CRC cells. Circ_0084188 acted as a sponge for miR-654-3p, and circ_0084188 regulated CRC cell behaviors via sponging miR-654-3p. Moreover, KLF12 was a target of miR-654-3p, and miR-654-3p overexpression inhibited the malignant behaviors of CRC cells by downregulating KLF12. Mechanically, circ_0084188 sponged miR-654-3p to regulate KLF12 expression in CRC cells. In addition, circ_0084188 downregulation inhibited tumor growth in vivo.Circ_0084188 knockdown might repress CRC progression partially via regulating the miR-654-3p/KLF12 axis, providing a novel insight into the pathogenesis of CRC.

Keywords: KLF12; circ_0084188; colorectal cancer; miR-654-3p.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Mice
  • MicroRNAs* / genetics
  • RNA, Circular / genetics

Substances

  • KLF12 protein, human
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • MIRN654 microRNA, human
  • RNA, Circular