Circ_0021087 acts as a miR-184 sponge and represses gastric cancer progression by adsorbing miR-184 and elevating FOSB expression

Eur J Clin Invest. 2021 Nov;51(11):e13605. doi: 10.1111/eci.13605. Epub 2021 Jun 2.

Abstract

Background: Gastric cancer (GC) ranks third among the causes of cancer-related deaths in the world. Circular RNA hsa_circ_0021087 (circ_0021087) plays a repressive role in GC. Nevertheless, the mechanism by which circ_0021087 constrains GC advancement is unclear.

Materials and methods: Expression patterns of circ_0021087, microRNA (miR)-184 and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) mRNA were assessed by quantitative real-time polymerase chain reaction (RT-qPCR). Gain-of-function experiments were conducted to verify the biological function of circ_0021087 in vitro and in vivo, including cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and xenograft assays. Protein levels were analysed by Western blotting and immunohistochemistry (IHC). The regulatory mechanism of circ_0021087 was analysed by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

Results and conclusion: Circ_0021087 and FOSB were lowly expressed in GC, whereas miR-184 had an opposite result. Circ_0021087 overexpression repressed GC cell proliferation and epithelial-mesenchymal transition (EMT) in xenograft models in vivo and induced GC cell apoptosis, repressed GC cell proliferation, EMT, migration and invasion in vitro. Circ_0021087 could elevate FOSB expression by adsorbing miR-184. MiR-184 mimic reversed the inhibitory influence of circ_0021087 overexpression on GC cell malignancy. Also, FOSB knockdown offset the suppressive impact of miR-184 silencing on GC cell malignancy. In conclusion, circ_0021087 played a repressive influence on GC progression by elevating FOSB expression by adsorbing miR-184, offering a new mechanism for circ_0021087 to inhibit the progression of GC.

Keywords: FOSB; GC; circ_0021087; miR-184.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism
  • Mice
  • MicroRNAs / metabolism*
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Circular / metabolism*
  • RNA, Messenger / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • FOSB protein, human
  • LIM Domain Proteins
  • LMO1 protein, human
  • MIRN184 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-fos
  • RNA, Circular
  • RNA, Messenger
  • Transcription Factors