circRNA_0006470 promotes the proliferation and migration of gastric cancer cells by functioning as a sponge of miR-27b-3p

Neoplasma. 2021 Nov;68(6):1245-1256. doi: 10.4149/neo_2021_210222N235. Epub 2021 Oct 10.

Abstract

Cancer pathogenesis is influenced by epigenetic alterations mediated by circular RNAs (circRNAs). In this study, we aimed to investigate the regulatory mechanisms and cytological function of hsa_circ_0006470/miR-27b-3p in gastric cancer (GC). circRNA and microRNA expressions in cancer cells were measured by the qRT-PCR method. A dual-luciferase reporter assay was performed to validate the binding of hsa_circ_0006470 with miR-27b-3p. hsa_circ_0006470 was silenced in AGS cells, and proliferation, migration, and invasion were tested via the CCK-8 assay and Transwell system, respectively. The autophagy in GC cells was assessed by marker protein detection and transmission electron microscope. The results showed that hsa_circ_0006470 expression was significantly elevated in GC cells, which was mainly distributed in cytoplasmic components and could directly bind with miR-27b-3p in GC cells. Silencing of hsa_circ_0006470 repressed cell proliferation, migration, and invasion, which may be through regulating miR-27b-3p/Receptor tyrosine kinase-like orphan receptor 1 (ROR1). Silencing of hsa_circ_0006470 also elevated LC3II and Beclin-1 and suppressed p62 protein abundances, which subsequently induced autophagy in AGS cells. Furthermore, we found that hsa_circ_0006470 promotes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) expressing by sponging miR-27b-3p. In conclusion, hsa_circ_0006470 promoted GC cell proliferation and migration through targeting miR-27b-3p and suppressing autophagy machinery.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • MicroRNAs* / genetics
  • RNA, Circular* / genetics
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Stomach Neoplasms* / genetics
  • Tumor Cells, Cultured

Substances

  • MIRN27 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • ROR1 protein, human
  • Receptor Tyrosine Kinase-like Orphan Receptors