Human mesenchymal stem cells derived exosomes inhibit the growth of acute myeloid leukemia cells via regulating miR-23b-5p/TRIM14 pathway

Mol Med. 2021 Oct 16;27(1):128. doi: 10.1186/s10020-021-00393-1.

Abstract

Background: Acute myeloid leukemia (AML) is a malignancy commonly seen in adults. Previous studies indicated that TRIM14 played a tumorigenic role in various types of cancer and miR-23b-5p was down-regulated in human mesenchymal stem cell-derived exosomes (HMSC-exos) of AML patients. However, their roles in AML remains unclear. Our study aims to investigate the role of TRIM14 and miR-23b-5p in the pathogenesis of AML.

Materials and methods: The blood specimen was collected from de novo AML patients and healthy donators. Exosomes were extracted from the culture medium of human mesenchymal stem cells under ultracentrifugation. Then exosomes were co-cultured with AML cells to determine the effect of their contents. The cell proliferation was detected by cell counting kit-8 assay, whereas the cell apoptosis was detected by flow cytometry. The expression of miR-23b-5p and TRIM14 was silenced or overexpressed to explore their biological functions in AML. Luciferase reporter assay was conducted to validate the interaction between miR-23b-5p and TRIM14. Gene expression was determined by quantitative real-time PCR and immunoblots.

Results: TRIM14 was significantly increased in AML patients and cell lines. The inhibition of TRIM14 significantly reduced the proliferation and induced the apoptosis of AML cells via activating PI3K/AKT pathway, whereas its overexpression exhibited reversed effects. HMSC-exos could suppress the proliferation of AML cells through the delivery of miR-23b-5p. Moreover, miR-23b-5p inhibited the transcription of TRIM14 by binding on its 3'UTR region. Overexpression of TRIM14 exhibited reversed effect against the function of miR-23b-5p mimic.

Conclusion: TRIM14 could promote the proliferation of AML cells via activating PI3K/AKT pathway, which was reversed by HMSC-exos through delivering miR-23b-5p. These findings indicated that miR-23b-5p and TRIM14 could be applied as potential targets for the treatment of AML.

Keywords: Acute myeloid leukemia; Exosomes; Human mesenchymal stem cell; TRIM14; miR-23b-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Acute Disease
  • Adult
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Exosomes / genetics*
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Leukemic*
  • HL-60 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • Middle Aged
  • RNA Interference
  • Signal Transduction / genetics
  • THP-1 Cells
  • Tripartite Motif Proteins / genetics*
  • Tripartite Motif Proteins / metabolism
  • Young Adult

Substances

  • 3' Untranslated Regions
  • Intracellular Signaling Peptides and Proteins
  • MIRN23b microRNA, human
  • MicroRNAs
  • TRIM14 protein, human
  • Tripartite Motif Proteins