The miR-146b-3p/TNFAIP2 axis regulates cell differentiation in acute myeloid leukaemia

Aging (Albany NY). 2024 Jan 24;16(2):1496-1515. doi: 10.18632/aging.205441. Epub 2024 Jan 24.

Abstract

Our purpose is to verify that miR-146b-3p targets the downstream transcript TNFAIP2 in order to reveal the machinery underlying the miR-146b-3p/TNFAIP2 axis regulating acute myeloid leukaemia (AML) differentiation. Bioinformatics analyses were performed using multiple databases and R packages. The CD11b+ and CD14+ cell frequencies were detected using flow cytometry and immunofluorescence staining. The TNFAIP2 protein expression was evaluated using western blotting, immunocytochemistry and immunofluorescence staining. The qRT-PCR was conducted to detect the expression of TNFAIP2 and miR-146b-3p. TNFAIP2 and its correlated genes were enriched in multiple cell differentiation pathways. TNFAIP2 was upregulated upon leukaemic cell differentiation. miR-146b-3p directly targeted TNFAIP2, resulting in a decrease in TNFAIP2 expression. Forced expression of TNFAIP2 or knockdown of miR-146b-3p significantly induced the differentiation of MOLM-13 cells. In this study, we demonstrated that TNFAIP2 is a critical driver in inducing differentiation and that the miR-146b-3p/TNFAIP2 axis involves in regulating cell differentiation in AML.

Keywords: AML; TNFAIP2; differentiation; mechanism; miR-146b-3p.

MeSH terms

  • Apoptosis / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cytokines* / genetics
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • MicroRNAs* / genetics

Substances

  • Cytokines
  • MicroRNAs
  • TNFAIP2 protein, human
  • MIRN146 microRNA, human