CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer

Pharmacol Res. 2024 Apr:202:107127. doi: 10.1016/j.phrs.2024.107127. Epub 2024 Mar 2.

Abstract

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Keywords: CircBIRC6; Gastric cancer; Grin2D.

MeSH terms

  • Autophagy
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • Caveolin 1
  • GRIN2D protein, human
  • MicroRNAs
  • MIRN488 microRNA, human
  • Receptors, N-Methyl-D-Aspartate
  • RNA, Circular
  • BIRC6 protein, human