胡恩赑,金 强,方福瑾.miR-15a在多发性骨髓瘤患者外泌体中的表达及外泌体对肿瘤生长的影响[J].肿瘤学杂志,2020,26(6):491-495. |
miR-15a在多发性骨髓瘤患者外泌体中的表达及外泌体对肿瘤生长的影响 |
Expression of miR-15a in Exosomes of Patients with Multiple Myeloma and the Effect of Exosomes on Tumor Cell Proliferation and Apoptosis |
投稿时间:2019-08-21 |
DOI:10.11735/j.issn.1671-170X.2020.06.B005 |
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中文关键词: 多发性骨髓瘤 外泌体 miR-15a Bcl-2 凋亡 |
英文关键词:multiple myeloma exosome miR-15a Bcl-2 apoptosis |
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中文摘要: |
摘 要:[目的] 探讨miR-15a在多发性骨髓瘤(MM)患者外泌体中的表达及外泌体对肿瘤发生发展的意义。[方法] 选择在我院治疗的MM患者71例及健康志愿者20例,分析miR-15a在血浆外泌体中的表达水平;并以人源MM细胞株MM.1R细胞为实验模型,采用增殖实验观察外泌体对肿瘤细胞增殖的影响,采用流式细胞术检测肿瘤细胞凋亡,采用Western blot检测凋亡通路相关蛋白的表达。[结果]与健康志愿者相比,MM患者的血浆miR-15a水平显著降低(4.45±0.20 vs 12.86±0.63,P<0.001),且与患者临床分期有关(P=0.023)。当使用MM患者来源的外泌体处理MM.1R细胞后,实验组细胞增殖率较对照组提高,在12h、24h、48h时分别提高了14.1%、34.0%、52.7%(P<0.01);而健康志愿者来源的外泌体则使细胞增殖率降低,在12h、24h、48h时分别降低了12.4%、20.8%、27.5% (P<0.01)。流式细胞术结果显示,MM患者来源外泌体抑制了肿瘤细胞凋亡,24h凋亡率减少了3.3% (P=0.005);而健康志愿者来源外泌体促进了肿瘤细胞凋亡,24h凋亡率增加了7.8% (P<0.001)。Western blot检测发现MM组的Bcl-2表达增加,Bax和caspase-3表达下降,与健康志愿者来源的外泌体作用相反。[结论]促凋亡因子miR-15a在MM患者外泌体中的表达水平低于健康人群,且MM患者来源的外泌体具有促进肿瘤发展的作用。 |
英文摘要: |
Abstract:[Objective] To investigate the expression levels of miR-15a in exosomes of patients with multiple myeloma(MM) and the effects of exosomes on apoptosis and proliferation of tumor cells. [Methods] The miR-15a levels in plasma exosomes of 20 healthy subjects and 71 MM patients were detected. A human MM cell line MM.1R was used as the experimental model to explore the effect of exosomes on tumor cell proliferation. The apoptosis of tumor cells was detected by flow cytometry,and the expression of proteins related to apoptosis pathways was detected by Western blot. [Results] Plasma miR-15a levels in MM patients was significantly decreased,compared with healthy subjects(4.45±0.20 vs 12.86±0.63,P<0.001);and it was associated with the clinical stages(P=0.023). When MM.1R cells were treated with exosomes from MM patients,the proliferation rate was higher than that of the PBS control group,increased by 14.1%,34.0% and 52.7% after 12h,24h and 48h of treatment,respectively(P<0.01). When MM.1R cells were treated with exosomes from healthy subjects,the proliferation rate reduced by 12.4%,20.8% and 27.5% after 12h,24h and 48h of treatment,respectively(P<0.01). Flow cytometry results showed that cell apoptosis was reduced by 3.3% after 24h treatment with exosomes from MM patients(P=0.005);cell apoptosis increased by 7.8% 24h after treatment with exosomes from healthy subjects(P<0.001). Western blot analysis showed that the expression of Bcl-2 increased,Bax and caspase-3 decreased in the MM group,which were contrary to the results of the control group. [Conclusion] The expression of miR-15a in exosomes of MM patients is down-regulated,and exosomes from MM patients can inhibit apoptosis and promote proliferation of MM cells. |
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