PMID- 32698859 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 39 IP - 1 DP - 2020 Jul 22 TI - Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression. PG - 140 LID - 10.1186/s13046-020-01631-w [doi] LID - 140 AB - 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. FAU - He, Zhanfeng AU - He Z AD - Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China. FAU - Li, Weihao AU - Li W AD - Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China. FAU - Zheng, Tianliang AU - Zheng T AD - Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China. FAU - Liu, Donglei AU - Liu D AD - Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China. FAU - Zhao, Song AU - Zhao S AD - Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China. zhaosong1963@yeah.net. LA - eng PT - Journal Article DEP - 20200722 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 RN - 0 (Biomarkers, Tumor) RN - 0 (Enah protein, human) RN - 0 (MIRN375 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Microfilament Proteins) SB - IM MH - Adult MH - Aged MH - Animals MH - Apoptosis MH - Biomarkers, Tumor/genetics/*metabolism MH - Cell Proliferation MH - Esophageal Neoplasms/genetics/metabolism/pathology/*therapy MH - Esophageal Squamous Cell Carcinoma/genetics/metabolism/pathology/therapy MH - Exosomes/*genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/*administration & dosage/genetics MH - Microfilament Proteins/genetics/*metabolism MH - Middle Aged MH - Prognosis MH - Survival Rate MH - Tumor Cells, Cultured MH - Umbilical Cord/cytology MH - Xenograft Model Antitumor Assays PMC - PMC7374920 OTO - NOTNLM OT - Enabled homolog OT - Esophageal squamous cell carcinoma OT - Exosomes OT - Human umbilical cord mesenchymal stem cells OT - microRNA-375 COIS- The authors declare that they have no conflict of interest. EDAT- 2020/07/24 06:00 MHDA- 2021/03/30 06:00 PMCR- 2020/07/22 CRDT- 2020/07/24 06:00 PHST- 2019/12/25 00:00 [received] PHST- 2020/06/29 00:00 [accepted] PHST- 2020/07/24 06:00 [entrez] PHST- 2020/07/24 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/07/22 00:00 [pmc-release] AID - 10.1186/s13046-020-01631-w [pii] AID - 1631 [pii] AID - 10.1186/s13046-020-01631-w [doi] PST - epublish SO - J Exp Clin Cancer Res. 2020 Jul 22;39(1):140. doi: 10.1186/s13046-020-01631-w.