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

Hui Cheng,Li Chen,Jianmin Yang,Jie Ding,Gusheng Tang,Lei Gao,Aijie Huang

doi:10.1186/s10020-021-00393-1

Hui Cheng, Li Chen + Show 5 more

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https://doi.org/10.1186/s10020-021-00393-1

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Abstract

BackgroundAcute 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 methodsThe 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.ResultsTRIM14 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.ConclusionTRIM14 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.

Highlights

Acute myeloid leukemia (AML) is a malignancy with the prompt growth of immature myeloid cells, which most commonly occurs in older adults and preferentially in males (De Kouchkovsky et al 2016)
Tripartite motif-containing 14 (TRIM14) promoted the proliferation and inhibited the apoptosis of AML To explore the role of TRIM14 in AML, we detected the expression of TRIM14 in the blood from 25 AML patients and healthy donators
Results indicated that three siRNAs could significantly reduce the expression of TRIM14 (p < 0.05) (Additional file 1: Fig. S1A–B), and TRIM14 was highly expressed after the transfection of overexpression plasmid (p < 0.05) (Additional file 1: Fig. S1C–D)

Summary

Introduction

Acute myeloid leukemia (AML) is a malignancy with the prompt growth of immature myeloid cells, which most commonly occurs in older adults and preferentially in males (De Kouchkovsky et al 2016). Previous studies indicated that the other members of the TRIM family such as TRIM31 and TRIM22 were associated with the progression and drug resistance of acute or chronic myeloid leukemia (Xiao et al 2020; Li et al 2018). 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. Our study aims to investigate the role of TRIM14 and miR-23b-5p in the pathogenesis of AML

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Conclusion