Repression of CRNDE enhances the anti-tumour activity of CD8 + T cells against oral squamous cell carcinoma through regulating miR-545-5p and TIM-3

J Cell Mol Med. 2021 Dec;25(23):10857-10868. doi: 10.1111/jcmm.16909. Epub 2021 Nov 2.

Abstract

Immunotherapy has been identified a promising treatment of cancers, including Oral squamous cell carcinoma (OSCC). CRNDE is highly overexpressed in various cancers. Many lncRNAs have been reported in CD8 T lymphocytes. Little is investigated about their effects in the functions of CD8 + T cells in OSCC. Currently, the influence of lncRNA CRNDE on the function of CD8 + T cells in OSCC progression was investigated. Here, CRNDE was obviously elevated and negatively correlated with IFN-γ production in tumour-infiltrating CD8 + T cells isolated from OSCC patients. CRNDE can exhibit a crucial role in activating CD8 + T-cell exhaustion. Mechanistically, CRNDE specifically sponged miR-545-5p to induce T-cell immunoglobulin and mucin domain-3 (TIM-3), thus contributing to CD8 + T-cell exhaustion. The function of miR-545-5p on T-cell function remains poorly known. TIM-3 is a significant immune checkpoint, and it inhibits cancer immunity. TIM-3 can demonstrate an important role in CD8 + T-cell exhaustion. In summary, loss of CRNDE could induce miR-545-5p and inhibit TIM3 expression, thus significantly activated the anti-tumour effect of CD8 + T cells.

Keywords: CRNDE; OSCC; TIM-3; immune response; miR-545-5p.

MeSH terms

  • Apoptosis / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Hepatocellular / immunology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Gene Expression Regulation, Neoplastic / immunology
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Liver Neoplasms / immunology
  • MicroRNAs / immunology*
  • Mouth Neoplasms / immunology*
  • RNA, Long Noncoding / immunology*
  • Squamous Cell Carcinoma of Head and Neck / immunology*

Substances

  • CRNDE RNA, human
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • MIR545 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding