Circ_0089761 accelerates colorectal cancer metastasis and immune escape via miR-27b-3p/PD-L1 axis

Physiol Rep. 2024 Nov;12(23):e70137. doi: 10.14814/phy2.70137.

Abstract

Circular RNAs have been implicated as critical regulators in the initiation and progression of colorectal cancer (CRC). This study was intended to elucidate the functional significance of the circ_0089761/miR-27b-3p/programmed cell death ligand 1 (PD-L1) axis in CRC. Our findings indicated that circ_0089761 expression was significantly elevated in CRC tissues and cell lines. Furthermore, the high expression of circ_0089761 was correlated with TNM stage and tumor size. Silencing circ_0089761 inhibited CRC cell proliferation, migration, and invasion, and increased apoptosis. Mechanistically, circ_0089761 facilitated its biological function by binding to miR-27b-3p to upregulate PD-L1 expression in CRC. Coculture experiments confirmed that low expression of circ_0089761 impeded CD8 + T cell apoptosis and depletion, activated CD8 + T cell function, and increased secretion of the immune effector cytokines IFN-γ, TNF-α, perforin, and granzyme-B. MiR-27b-3p inhibition or PD-L1 overexpression partially impeded CD8 + T cell function. The circ_0089761/miR-27b-3p/PD-L1 axis is postulated to exert pivotal functions in the mechanistic progression of CRC. Furthermore, it holds promising prospects as a feasible biomarker and therapeutic target for CRC.

Keywords: PD‐L1; circ_0089761; colorectal cancer; miR‐27b‐3p.

MeSH terms

  • Apoptosis
  • B7-H1 Antigen* / genetics
  • B7-H1 Antigen* / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • Tumor Escape / genetics

Substances

  • MicroRNAs
  • B7-H1 Antigen
  • RNA, Circular
  • CD274 protein, human
  • MIRN27b microRNA, human