PMID- 33206588 OWN - NLM STAT- MEDLINE DCOM- 20220301 LR - 20220301 IS - 1555-8584 (Electronic) IS - 1547-6286 (Print) IS - 1547-6286 (Linking) VI - 18 IP - 10 DP - 2021 Oct TI - Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10. PG - 1408-1423 LID - 10.1080/15476286.2020.1851540 [doi] AB - Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs (miRNAs) have been highlighted in human cancers. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-451a on hepatocellular carcinoma (HCC) remains further investigation. Our study aims to explore the impact of exosomal miR-451a on the progression of HCC. Expression of miR-451a and a disintegrin and metalloprotease 10 (ADAM10) in HCC tissues and adjacent normal tissues were determined. The exosomes were extracted from hucMSCs and co-cultured with Hep3B and SMMC-7721 cell lines. After the treatment of relative exosomes or exosome inhibitor GW4869 in Hep3B and SMMC-7721 cells, the paclitaxel resistance and malignant phenotypes of HCC cells were measured. Moreover, the effect of hucMSCs-derived exosomes on the expression of miR-451a and ADAM10 in HCC cells was assessed. The targeting relationship between miR-451a and ADAM10 was verified to detect the impact of ADAM10-wild type and ADAM10-mutant type (MUT) on HCC cell processes. Low expression of miR-451a and high expression of ADAM10 indicated a poor prognosis of HCC patients. MiR-451a was up-regulated while ADAM10 was down-regulated in HCC cells after co-culture with HucMSC-derived exosomes. The exosomes elevated miR-451a and inhibited ADAM10 to suppress the paclitaxel resistance, cell cycle transition, proliferation, migration and invasion, and promote apoptosis of HCC cells. ADAM10 was verified to be a target gene of miR-451a. ADAM10-MUT promoted HCC process independent of miR-451a mimic. HucMSC-derived exosomal miR-451a could restrict the epithelial-mesenchymal transition of HCC cells by targeting ADAM10, which might provide new targets for HCC treatment. FAU - Xu, Yunxiuxiu AU - Xu Y AD - Department of Hepato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Lai, Yu AU - Lai Y AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Cao, Linhui AU - Cao L AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Department of Traditional Chinese Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Li, Yanshan AU - Li Y AD - Department of Blood Transfusion, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Chen, Guangcheng AU - Chen G AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Chen, Liang AU - Chen L AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Department of Intensive Care Unit, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Weng, Hanqin AU - Weng H AD - Department of Hepato-Billiary Surgery, Dongguan people's Hospital, Southern Medical University, Guangdong, China. FAU - Chen, Tao AU - Chen T AD - Department of Hepato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Wang, Lingyun AU - Wang L AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. FAU - Ye, Yibiao AU - Ye Y AD - Department of Hepato-Billiary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. AD - Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201231 PL - United States TA - RNA Biol JT - RNA biology JID - 101235328 RN - 0 (Aniline Compounds) RN - 0 (Benzylidene Compounds) RN - 0 (GW 4869) RN - 0 (MIRN451 microRNA, human) RN - 0 (Membrane Proteins) RN - 0 (MicroRNAs) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.24.81 (ADAM10 Protein) RN - EC 3.4.24.81 (ADAM10 protein, human) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - ADAM10 Protein/*genetics MH - Adult MH - Aged MH - Amyloid Precursor Protein Secretases/*genetics MH - Aniline Compounds/pharmacology MH - Benzylidene Compounds/pharmacology MH - Carcinoma, Hepatocellular/genetics/*pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Coculture Techniques MH - *Drug Resistance, Neoplasm MH - Epithelial-Mesenchymal Transition MH - Exosomes/drug effects/*genetics MH - Female MH - Gene Expression Regulation, Neoplastic MH - Hep G2 Cells MH - Humans MH - Liver Neoplasms/genetics/*pathology MH - Male MH - Membrane Proteins/*genetics MH - Mesenchymal Stem Cells/chemistry/cytology MH - MicroRNAs/*genetics MH - Middle Aged MH - Paclitaxel/pharmacology MH - Prognosis MH - Survival Analysis MH - Umbilical Cord/chemistry/*cytology PMC - PMC8489916 OTO - NOTNLM OT - Hepatocellular carcinoma OT - MicroRNA-451a OT - a disintegrin and metalloprotease 10 OT - exosome OT - human umbilical cord mesenchymal stem cells COIS- The authors declare that they have no conflicts of interest. EDAT- 2020/11/19 06:00 MHDA- 2022/03/03 06:00 PMCR- 2021/12/31 CRDT- 2020/11/18 17:09 PHST- 2020/11/19 06:00 [pubmed] PHST- 2022/03/03 06:00 [medline] PHST- 2020/11/18 17:09 [entrez] PHST- 2021/12/31 00:00 [pmc-release] AID - 1851540 [pii] AID - 10.1080/15476286.2020.1851540 [doi] PST - ppublish SO - RNA Biol. 2021 Oct;18(10):1408-1423. doi: 10.1080/15476286.2020.1851540. Epub 2020 Dec 31.