Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression

Eur J Clin Invest. 2021 Nov;51(11):e13592. doi: 10.1111/eci.13592. Epub 2021 May 25.

Abstract

Background: Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression.

Methods: The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay.

Results: Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo.

Conclusion: Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.

Keywords: RUNX1; circ_0027599; gastric cancer; miR-21-5p.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cadherins / metabolism
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA, Circular / metabolism*
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Core Binding Factor Alpha 2 Subunit
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger
  • RUNX1 protein, human
  • VIM protein, human
  • Vimentin