Hsa_circ_0000285 contributes to gastric cancer progression by upregulating FN1 through the inhibition of miR-1278

J Clin Lab Anal. 2022 Jun;36(6):e24475. doi: 10.1002/jcla.24475. Epub 2022 May 9.

Abstract

Background: Gastric cancer (GC) is one of the most severe cancers worldwide, particularly in China. Circular RNA (circRNA) plays an essential role in GC. Hsa_circ_0000285 regulates the progression of several cancers. However, its role in GC has not been reported. This study elucidated the molecular mechanism and role of hsa_circ_0000285 in GC progression.

Methods: GC cells were transfected with silencers of hsa_circ_0000285 and fibronectin 1 (FN1), an inhibitor of miR-1278, and their negative controls (NC). Mice were injected with short hairpin (sh) RNAs targeting hsa_circ_0000285 or NC. The expression levels of hsa_circ_0000285, miR-1278, and FN1 were assessed using western blotting and reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). Several assays were used to evaluate cell proliferation, invasion, and apoptosis. Tumor burden was also analyzed. The interactions between miR-1278, hsa_circ_0000285, and FN1 were ascertained using dual-luciferase reporter assays. An RNA immunoprecipitation (RIP) assay was used to assess the enrichment of hsa_circ_0000285 and miR-1278 in GC.

Results: Hsa_circ_0000285 was significantly overexpressed in the GC tissues. Silencing hsa_circ_0000285 inhibited cell proliferation and invasion, promoted apoptosis, and inhibited tumor development. Hsa_circ_0000285 sponged miR-1278. Inhibition of miR-1278 in vitro reversed the effects of hsa_circ_0000285 silencing on GC progression. MiR-1278 targeted FN1, and silencing FN1 neutralized the effects of miR-1278 inhibitors on GC progression.

Conclusions: The hsa_circ_0000285/miR-1278/FN1 axis regulated GC progression. In addition, it may serve as a potential therapeutic biomarker for GC.

Keywords: FN1; circRNA; gastric cancer; hsa_circ_0000285; miR-1278.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Fibronectins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • Fibronectins
  • MicroRNAs