CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2.
Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2.
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骨髓间充质干细胞（BMSC）是多发性骨髓瘤（MM）微环境的重要组成部分，并支持MM的恶性进展。BMSC是否通过外泌体作用于MM细胞尚未得到充分表征。
在此，我们使用微阵列筛选来自MM患者（MM-MSC）或良性疾病患者（BD-MSC）的BMSC中差异表达的miRNA。我们发现miR-483-5p在MM-MSC中高表达，其可能通过外泌体从MM-MSC转运至MM细胞，从而增加MM细胞中miR-483-5p的表达。随后我们在体外研究了miR-483-5p在MM侵袭性进展中的作用和机制。
我们证实miR-483-5p促进MM细胞增殖并减少凋亡。接着我们预测并验证了TIMP2，一个抑癌基因，是MM中miR-483-5p的下游靶点。
总之，我们的研究表明MM-MSC通过释放外泌体和调控miR-483-5p/TIMP2轴促进MM恶性进展，提示BMSC来源的外泌体miRNA在MM中的重要作用以及作为MM诊断和治疗潜在标志物的可能性。
Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized.
Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs).
We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them.
We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro .
We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.
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