Circulating miR-221/222 reduces CD4+ T cells by inhibiting CD4 expression in colorectal cancer

Acta Biochim Biophys Sin (Shanghai). 2021 Oct 12;53(10):1367-1376. doi: 10.1093/abbs/gmab106.

Abstract

Many patients with cancers have low levels of CD4+ in their peripheral blood. However, the molecular mechanism is still unclear. Here, we found that the blood levels of miR-221 and miR-222 were dramatically increased in patients with colorectal cancer (CRC), and both circulating miR-211 and miR-222 served as sensitive diagnostic markers with an area under the curve of 0.8790 and 0.9148, respectively. Transfection of either miR-221 or miR-222 resulted in the reduction of the surface CD4 antigen level but not the surface CD8 antigen level. The luciferase reporter assay showed that miR-221/222 directly regulated CD4 expression in human primary T cells. These data showed that miR-221/222 levels were upregulated in the blood of patients with CRC and that the expression of CD4 in human primary T cells was inhibited by miR-221/222. These findings provide a novel strategy for modulating the number of CD4+ T cells in the blood and further adjusting the microenvironment suitable for immunotherapy.

Keywords: CD4; CD8; colorectal cancer; immunotherapy; miR-221; miR-222.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / immunology*
  • MicroRNAs / metabolism
  • Middle Aged
  • ROC Curve
  • Up-Regulation

Substances

  • CD4 Antigens
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs