CircRNA-ABCB10 promotes gastric cancer progression by sponging miR-1915-3p to upregulate RaC1

Dig Liver Dis. 2022 Jul;54(7):896-904. doi: 10.1016/j.dld.2021.12.001. Epub 2022 Jan 3.

Abstract

Background: Gastric cancer (GC) is a common malignant tumor of the digestive system. Increasing reports have demonstrated the crucial roles of circRNAs in tumorigenesis and progression of GC.

Methods: The relative expression of circ-ABCB10 in GC tissues and cell lines was detected by qRT-PCR. A series of in vitro assays and a xenograft model in vivo were applied to explore the function of circ-ABCB10 in GC cells.

Results: Circ-ABCB10 expression was upregulated in GC tissues and cell lines and positively correlated with poor survival of GC patients. Circ-ABCB10 downregulation decreased cell viability, inhibited cell growth, invasion, and migration, while promoted cell apoptosis of GC cell lines SGC-7901 and MKN-48. Circ-ABCB10 could upregulate Rac1 expression by directly sponging miR-1915-3p. Rescue experiments revealed that miR-1915-3p inhibitor obviously reversed the inhibitory effect of si-circ-ABCB10, and Rac1 overexpression obviously reversed the inhibitory effect of miR-1915-3p mimics on cell growth, invasion, migration, apoptosis, and cell cycle progression. Moreover, si-circ-ABCB10 effectively inhibited tumor growth in a xenograft model.

Conclusions: Our study revealed that circ-ABCB10 promoted GC progression via targeting the miR-1915-3p/Rac1 axis, and circ-ABCB10 might be a potential target for GC diagnosis and treatment.

Keywords: Circ-ABCB10; Gastric cancer; Rac1; Tumorigenesis; miR-1915–3p.

MeSH terms

  • ATP-Binding Cassette Transporters* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Stomach Neoplasms* / pathology
  • rac1 GTP-Binding Protein* / genetics
  • rac1 GTP-Binding Protein* / metabolism

Substances

  • ABCB10 protein, human
  • ATP-Binding Cassette Transporters
  • MIRN1915 microRNA, human
  • MicroRNAs
  • RAC1 protein, human
  • RNA, Circular
  • rac1 GTP-Binding Protein