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Exosomes derived from human bone marrow mesenchymal stem cells transfer miR-222-3p to suppress acute myeloid leukemia cell proliferation by targeting IRF2/INPP4B.
Molecular and Cellular Probes ( IF 3.3 ) Pub Date : 2020-01-20 , DOI: 10.1016/j.mcp.2020.101513
Feng Zhang 1 , Yaqin Lu 2 , Meng Wang 1 , Junfeng Zhu 1 , Jiajia Li 1 , Pingping Zhang 1 , Yuan Yuan 1 , Fangbing Zhu 1
Affiliation  

AIM This study aims to explore the role and mechanism of exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs-Exo) in regulating proliferation and apoptosis of acute myeloid leukemia (AML) cell line THP-1. METHODS hBM-MSCs-Exo was isolated by ultra-centrifugation and administered into THP-1 cells to elucidate the effects of exosomes in THP-1 cells. Cell proliferation and apoptosis were examined by CCK-8 assay and flow cytometry, respectively. The expression of miR-222-3p, IRF2, and INPP4B were measured by qRT-PCR and western blot. The interaction between miR-222-3p and IRF2 was analyzed by luciferase reporter assay. RESULTS Lower cell viability rate, higher apoptosis ratio, higher miR-222-3p expression, and lower IRF1/INPP4B expression were observed in THP-1 cells exposed to BM-MSCs-Exo. The proliferation-inhibitory and pro-apoptotic effects of BM-MSCs-Exo on THP-1 cells were markedly compromised when miR-222-3p expression in BM-MSCs-Exo was inhibited. Furthermore, miR-222-3p directly targeted IRF2 and negatively regulated IRF2/INPP4B signaling in THP-1 cells. Moreover, overexpression of either IRF2 or INPP4B counteracted the proliferation-inhibitory and pro-apoptotic effects mediated by BM-MSCs-Exo. CONCLUSION BM-MSCs delivered miR-222-3p via exosomes to inhibit cell proliferation and promote cell apoptosis by targeting IRF2 and negatively regulating IRF2/INPP4B signaling in THP-1 cells.

中文翻译:

来自人骨髓间充质干细胞的外泌体通过靶向IRF2 / INPP4B转移miR-222-3p以抑制急性髓性白血病细胞增殖。

目的本研究旨在探讨人骨髓间充质干细胞(hBM-MSCs-Exo)衍生的外泌体在调节急性髓系白血病(AML)细胞系THP-1增殖和凋亡中的作用和机制。方法通过超速离心分离hBM-MSCs-Exo,将其注入THP-1细胞,以阐明外泌体在THP-1细胞中的作用。通过CCK-8测定和流式细胞术分别检查细胞增殖和凋亡。通过qRT-PCR和Western blot检测miR-222-3p,IRF2和INPP4B的表达。miR-222-3p和IRF2之间的相互作用通过荧光素酶报告基因分析进行了分析。结果在暴露于BM-MSCs-Exo的THP-1细胞中观察到较低的细胞存活率,较高的凋亡率,较高的miR-222-3p表达和较低的IRF1 / INPP4B表达。当抑制BM-MSCs-Exo中的miR-222-3p表达时,BM-MSCs-Exo对THP-1细胞的增殖抑制和促凋亡作用明显减弱。此外,miR-222-3p在THP-1细胞中直接靶向IRF2,并负调控IRF2 / INPP4B信号。此外,IRF2或INPP4B的过表达抵消了BM-MSCs-Exo介导的增殖抑制和促凋亡作用。结论BM-MSC通过外泌体传递miR-222-3p,通过靶向IRF2并负调控THP-1细胞中的IRF2 / INPP4B信号传导来抑制细胞增殖并促进细胞凋亡。此外,IRF2或INPP4B的过表达抵消了BM-MSCs-Exo介导的增殖抑制和促凋亡作用。结论BM-MSC通过外泌体传递miR-222-3p,通过靶向IRF2并负调控THP-1细胞中的IRF2 / INPP4B信号传导来抑制细胞增殖并促进细胞凋亡。此外,IRF2或INPP4B的过表达抵消了BM-MSCs-Exo介导的增殖抑制和促凋亡作用。结论BM-MSC通过外泌体传递miR-222-3p,通过靶向IRF2并负调控THP-1细胞中的IRF2 / INPP4B信号传导来抑制细胞增殖并促进细胞凋亡。
更新日期:2020-01-20
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