CircNFIX knockdown inhibited AML tumorigenicity by the miR-876-3p/TRIM31 axis

Hematology. 2022 Dec;27(1):1046-1055. doi: 10.1080/16078454.2022.2115699.

Abstract

Background: Acute myeloid leukemia (AML) is one of the most common malignant myeloid diseases in adults with a dismal prognosis. We aimed to explore the effects of circNFIX on the proliferation and apoptosis of AML cells.

Methods: The expressions of circNFIX, miR-876-3p and tripartite motif (TRIM) 31 in the bone marrow specimens of AML patients and AML cell lines were detected by qRT-PCR or western blot. Cell proliferation was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-ethynyl-29-deoxyuridine (EdU) assays. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was used to detect protein expression. The relationship between miR-876-3p and circNFIX or TRIM31 was identified by dual-luciferase reporter assay or RNA pull-down assay.

Results: The expression level of circNFIX was significantly increased in the bone marrow samples of AML patients and AML cells when compared with normal controls. CircNFIX silencing inhibited AML cell proliferation and promoted apoptosis. Inhibition of miR-876-3p reversed the effect of circNFIX knockdown on AML cell progression. In addition, circNFIX indirectly regulated TRIM31 through miR-876-3p. Further, TRIM31 overexpression counteracted the effect of circNFIX silencing on AML cell proliferation and apoptosis.

Conclusion: CircNFIX knockdown could suppress the proliferation and induce the apoptosis of AML cells by targeting the miR-876-3p/TRIM31 axis.

Keywords: AML; AML cells; Acute myeloid leukemia; FITC; NSCLC; TRIM31; circNFIX; miR-876-3p.

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Humans
  • Leukemia, Myeloid, Acute* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases

Substances

  • MIRN876 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Tripartite Motif Proteins
  • TRIM31 protein, human
  • Ubiquitin-Protein Ligases