Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression
Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression
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人脐带间充质干细胞来源的exosomes递送microRNA-375以下调ENAH并因此延缓食管鳞状细胞癌进展
DOI：
10.1186/s13046-020-01631-w
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发表时间：
2020-07-22
影响因子：
11.3
通讯作者：
Zhao, Song
中科院分区：
文献类型：
--
作者：
He, Zhanfeng;Li, Weihao;Zhao, Song
背景来源于骨髓间充质干细胞（UCMSCs）的外泌体microRNA（miRNAs或miRs）已成为癌症治疗的有前景的治疗策略。本研究旨在阐明人脐带间充质干细胞（human umbilical cord mesenchymal stem cells，hUCMSCs）来源的exosomal miR-375在食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）中的作用机制。方法通过检测miR-375及其靶向同源物（ENAH）在食管鳞癌组织和细胞中的表达，分析其表达改变对食管鳞癌增殖、侵袭、迁移及肿瘤球形成的影响。分离转染的hUCMSCs衍生的外泌体（hUCMSCs-exo）并与ESCC细胞共培养以测量由hUCMSCs-exo递送的miR-375对ESCC发展的影响。最后，我们研究了miR-375对体内肿瘤生长的影响。结果食管鳞癌组织中miR-375表达降低，ENAH表达升高。ENAH被鉴定为miR-375的靶基因。miR-375表达升高或ENAH表达缺失抑制ESCC细胞增殖、侵袭、迁移、肿瘤球形成，并促进凋亡。hUCMSCs-exo介导的miR-375在体外可抑制食管鳞癌细胞的增殖、侵袭、迁移和肿瘤球形成，但在体内可抑制肿瘤生长，促进细胞凋亡。结论hUCMSCs-exo可通过转染miR-375抑制ENAH的表达，从而抑制食管鳞癌的发生和发展。
Background Exosomal microRNAs (miRNAs or miRs) from bone marrow-derived mesenchymal stem cells (UCMSCs) have emerged as promising therapeutic strategies for cancer treatment. The current study aimed to elucidate the underlying mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomal miR-375 in esophageal squamous cell carcinoma (ESCC). Methods After determining the expression of miR-375 and its putative target enabled homolog (ENAH) in ESCC tissues and cells, we tested effects of their altered expression on ESCC proliferation, invasion, migration, and tumorsphere formation was subsequently measured. Transfected hUCMSCs-derived exosomes (hUCMSCs-exo) were isolated and co-cultured with ESCC cells to measure the effects of miR-375 delivered by hUCMSCs-exo on ESCC development. Finally, we investigated the effect of miR-375 on tumor growth in vivo. Results The expression of miR-375 was reduced, while the expression of ENAH was elevated in ESCC. ENAH was identified as a target gene of miR-375. Elevated miR-375 or depleted ENAH expression inhibited ESCC cell proliferation, invasion, migration, tumorsphere formation, and promoted apoptosis. Moreover, miR-375 delivered by hUCMSCs-exo could suppress ESCC cell proliferation, invasion, migration, tumorsphere formation, but promoted apoptosis in vitro, as well as inhibiting tumor growth in vivo. Conclusions Taken together, hUCMSCs-exo can deliver miR-375 to suppress ENAH expression and subsequently inhibit the initiation and progression of ESCC.