Hematology Department, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Cardiac and Vascular Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
J Healthc Eng. 2021 Nov 19;2021:9457070. doi: 10.1155/2021/9457070. eCollection 2021.
Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried by HLAL-derived exosomes, on the hematopoietic function of HSCs and BM-MSCs. For this purpose, we have isolated exosomes from the peripheral blood of HLAL patients and healthy volunteers. Then, we measured the level of miR-125b in exosomes cocultured exosomes with HSCs and BM-MSCs. Moreover, we have used miR-125b inhibitors/mimic for intervention and then measured miR-125b expression and colony forming unit (CFU). Apart from it, HSC and BM-MSC hematopoietic-related factors -globulin, -globulin, CSF2, CRTX4 and CXCL12, SCF, IGF1, and DKK1 expression were measured. Evaluation of the miR-125b and BAK1 targeting relationship, level of miR-125b, and expression of hematopoietic-related genes was performed after patients are treated with miR-125b mimic and si-BAK1. We have observed that miR-125b was upregulated in HLAL-derived exosomes. After HLAL-exosome acts on HSCs, the level of miR-125b is upregulated, reducing CFU and affecting the expression of -globulin, -globulin, CSF2, and CRCX4. For BM-MSCs, after the action of HLAL-exo, the level of miR-125b is upregulated and affected the expression of CXCL12, SCF, IGF1, and DKK1. Exosomes derived from HLAL carry miR-125b to target and regulate BAK1. Further study confirmed that miR-125b and BAK1mimic reduced the expression of miR-125b and reversed the effect of miR-125b mimic on hematopoietic-related genes. These results demonstrated that HLAL-derived exosomes carrying miR-125b inhibit the hematopoietic differentiation of HSC and hematopoietic support function of BM-MSC through BAK1.
高白细胞急性白血病 (HLAL) 循环外泌体被递送至造血干细胞 (HSCs) 和骨髓间充质干细胞 (BM-MSCs)，从而抑制正常的造血过程。在本文中，我们评估并探讨了 HLAL 衍生外泌体携带的 miR-125b 对 HSCs 和 BM-MSCs 造血功能的影响。为此，我们从 HLAL 患者和健康志愿者的外周血中分离出外泌体，然后测量共培养外泌体与 HSCs 和 BM-MSCs 时外泌体中的 miR-125b 水平。此外，我们使用 miR-125b 抑制剂/模拟物进行干预，然后测量 miR-125b 表达和集落形成单位 (CFU)。除此之外，还测量 HSC 和 BM-MSC 造血相关因子 -球蛋白、-球蛋白、CSF2、CRTX4 和 CXCL12、SCF、IGF1 和 DKK1 的表达。评估 miR-125b 和 BAK1 的靶向关系、miR-125b 水平和造血相关基因的表达，然后对患者进行 miR-125b 模拟物和 si-BAK1 治疗。我们观察到 HLAL 衍生的外泌体中 miR-125b 上调。HLAL-外泌体作用于 HSCs 后，miR-125b 水平上调，降低 CFU，并影响 -球蛋白、-球蛋白、CSF2 和 CRCX4 的表达。对于 BM-MSCs，HLAL-exo 作用后，miR-125b 水平上调，影响 CXCL12、SCF、IGF1 和 DKK1 的表达。HLAL 衍生的外泌体携带 miR-125b 以靶向和调节 BAK1。进一步的研究证实，miR-125b 和 BAK1 模拟物降低了 miR-125b 的表达，并逆转了 miR-125b 模拟物对造血相关基因的作用。这些结果表明，HLAL 衍生的外泌体携带 miR-125b 通过 BAK1 抑制 HSC 的造血分化和 BM-MSC 的造血支持功能。
