Human bone marrow mesenchymal stem cell-derived extracellular vesicles impede the progression of cervical cancer via the miR-144-3p/CEP55 pathway.
Human bone marrow mesenchymal stem cell-derived extracellular vesicles impede the progression of cervical cancer via the miR-144-3p/CEP55 pathway.
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人骨髓间充质干细胞衍生的细胞外囊泡通过miR-144- 3 p/CEP 55通路阻止宫颈癌的进展
DOI：
10.1111/jcmm.15573
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Meng Q;Zhang B;Zhang Y;Wang S;Zhu X
宫颈癌是妇科最常见的恶性肿瘤，在中年女性中发病率和死亡率较高。人骨髓间充质干细胞(HBMSCs)参与了肿瘤的发生和发展，细胞外小泡(EV)通过传递microRNAs(miRNAs或miRs)介导细胞内的通讯。本研究旨在探讨hBMSCs来源的EVS包裹的miR-144-3p可能介导宫颈癌进展的生理机制。RT-qPCR和Western印迹分析检测中心体蛋白55kD(CEP55)和miR-144-3p在宫颈癌细胞株和组织中的表达。通过计算机分析和荧光素酶活性测定，鉴定miR-144-3p与CEP55的结合亲和力。将宫颈癌细胞与经miR-144-3p模拟物或miR-144-3p抑制剂处理的hBMSCs来源的EV共培养。体外检测宫颈癌细胞的增殖、侵袭、迁移和凋亡情况。并观察了hBMSCs-miR-144-3p对肿瘤生长的影响。在宫颈癌细胞系和组织中，MIR-144-3p表达下调，而CEP55表达上调。CEP55是miR-144-3p的靶点，通过抑制宫颈癌细胞的增殖、侵袭和迁移，促进细胞的凋亡。此外，携带miR-144-3p的人骨髓间充质干细胞来源的EV也得到了类似的结果。体内实验证实了miR-144-3p在hBMSCs来源的EVS中对宫颈癌的抑制作用。总之，hBMSCs来源的EVS负载miR-144-3p通过靶向抑制CEP55来阻止宫颈癌的发生和发展，从而为我们提供了治疗宫颈癌的潜在靶点。
Cervical cancer is the most common gynaecological malignancy, with a high incidence rate and mortality rate in middle‐aged women. Human bone marrow mesenchymal stem cells (hBMSCs) have been implicated in the initiation and subsequent development of cancer, along with the involvement of extracellular vesicles (EVs) mediating intracellular communication by delivering microRNAs (miRNAs or miRs). This study is aimed at investigating the physiological mechanisms by which EVs‐encapsulated miR‐144‐3p derived from hBMSCs might mediate the progression of cervical cancer. The expression profiles of centrosomal protein, 55 Kd (CEP55) and miR‐144‐3p in cervical cancer cell lines and tissues, were quantified by RT‐qPCR and Western blot analysis. The binding affinity between miR‐144‐3p and CEP55 was identified using in silico analysis and luciferase activity determination. Cervical cancer cells were co‐cultured with EVs derived from hBMSCs that were treated with either miR‐144‐3p mimic or miR‐144‐3p inhibitor. Cervical cancer cell proliferation, invasion, migration and apoptosis were detected in vitro. The effects of hBMSCs‐miR‐144‐3p on tumour growth were also investigated in vivo. miR‐144‐3p was down‐regulated, whereas CEP55 was up‐regulated in cervical cancer cell lines and tissues. CEP55 was targeted by miR‐144‐3p, which suppressed cervical cancer cell proliferation, invasion and migration and promoted apoptosis via CEP55. Furthermore, similar results were obtained by hBMSCs‐derived EVs carrying miR‐144‐3p. In vivo assays confirmed the tumour‐suppressive effects of miR‐144‐3p in hBMSCs‐derived EVs on cervical cancer. Collectively, hBMSCs‐derived EVs‐loaded miR‐144‐3p impedes the development and progression of cervical cancer through target inhibition of CEP55, therefore providing us with a potential therapeutic target for treating cervical cancer.
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DOI：
10.1186/s13046-017-0504-6
发表时间：
2017-03-07
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
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通讯作者：
Su C
影响因子：
3.5
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DOI：
10.26355/eurrev_201811_16252
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2018-11-01
影响因子：
3.3
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通讯作者：
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影响因子：
6.4
作者：
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影响因子：
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