Cervical cancer is the most prevalent gynecological malignancies accompanied by high mortality, where finding a more effective therapeutic option for cervical cancer is necessary. The inhibitory role of microRNAs (miRNAs) derived from the extracellular vesicles (EVs) of the bone marrow mesenchymal stem cells (BMSCs) was analyzed in cervical cancer. Expression of miR-375 was examined by RT-qPCR in cervical cancer cell lines. The targeting relation between miR-375 and maternal embryonic leucine zipper kinase (MELK) was predicted by bioinformatics analysis and verified by dual-luciferase reporter gene assay. Isolated BMSCs were transfected with lentivirus-mediated vectors, followed by EV extraction. The morphology of EVs was then identified using a NanoSight particle size analyzer and transmission electron microscope (TEM). The biological properties of cervical cancer cells were evaluated using Transwell, EdU, and TUNEL assays, respectively. Xenograft tumors in nude mice were observed to assess cervical tumorigenesis in vivo. Low expression of miR-375 and high expression of MELK were detected in cervical cancer samples. MELK was identified as the target gene of miR-375, which was negatively correlated with miR-375 levels. Overexpression of miR-375 suppressed proliferation, migration, and invasion of cervical cancer cells, but enhanced cell apoptosis by cooperating with downregulated MELK expression. miR-375 transferred from BMSC-derived EVs exerted the same effects on cell biological activities. Xenograft assays in vivo proved that miR-375 from BMSC-derived EVs inhibited tumor growth. The present study highlighted the role of miR-375 from BMSC-derived EVs in suppressing the progression of cervical cancer, which may contribute to the discovery of novel potential biomarkers for cervical cancer therapy.

中文翻译：

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骨髓间充质干细胞胞外囊泡释放的 microRNA-375 对宫颈癌具有抗癌作用

宫颈癌是最常见的妇科恶性肿瘤，死亡率高，寻找更有效的宫颈癌治疗方案势在必行。分析了源自骨髓间充质干细胞 (BMSCs) 的细胞外囊泡 (EVs) 的 microRNA (miRNA) 在宫颈癌中的抑制作用。通过 RT-qPCR 在宫颈癌细胞系中检测 miR-375 的表达。通过生物信息学分析预测miR-375与母体胚胎亮氨酸拉链激酶（MELK）之间的靶向关系，并通过双荧光素酶报告基因测定进行验证。用慢病毒介导的载体转染分离的 BMSC，然后提取 EV。然后使用 NanoSight 粒度分析仪和透射电子显微镜 (TEM) 鉴定 EV 的形态。分别使用 Transwell、EdU 和 TUNEL 测定法评估宫颈癌细胞的生物学特性。观察裸鼠异种移植肿瘤以评估体内宫颈肿瘤发生。在宫颈癌样本中检测到 miR-375 的低表达和 MELK 的高表达。melk被确定为mir-375的靶基因，与mir-375水平呈负相关。miR-375的过表达抑制了宫颈癌细胞的增殖、迁移和侵袭，但通过与下调的MELK表达协同作用增强了细胞凋亡。从 BMSC 衍生的 EV 转移的 miR-375 对细胞生物活性产生了相同的影响。体内异种移植试验证明来自 BMSC 衍生的 EV 的 miR-375 抑制了肿瘤生长。