PMID- 31186161 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20211204 IS - 1673-8527 (Print) IS - 1673-8527 (Linking) VI - 46 IP - 5 DP - 2019 May 20 TI - mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3beta/MMPs. PG - 235-245 LID - S1673-8527(19)30085-2 [pii] LID - 10.1016/j.jgg.2019.03.013 [doi] AB - Golgi membrane protein 1 (GOLM1/GP73) is a serum marker of hepatocellular carcinoma (HCC). We have previously shown that mTOR promoted tumorigenesis of HCC through stimulating GOLM1 expression. In this study, we demonstrated that the mammalian target of rapamycin (mTOR) was a negative regulator of microRNA-145 (miR-145) expression. miR-145 inhibited GOLM1 expression by targeting a coding sequence of GOLM1 gene. GOLM1 and miR-145 were inversely correlated in human HCC tissues. GOLM1-enriched exosomes activated the glycogen synthase kinase-3beta/matrix metalloproteinases (GSK-3beta/MMPs) signaling axis of recipient cells and accelerated cell proliferation and migration. In contrast, miR-145 suppressed tumorigenesis and metastasis. We suggest that mTOR/miR-145/GOLM1 signaling pathway should be targeted for HCC treatment. CI - Copyright (c) 2019 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved. FAU - Gai, Xiaochen AU - Gai X AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. FAU - Tang, Bufu AU - Tang B AD - First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China; Department of Radiology, Lishui Hospital of Zhejiang University, Lishui, 323000, China; Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 323000, China. FAU - Liu, Fangming AU - Liu F AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. FAU - Wu, Yuting AU - Wu Y AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. FAU - Wang, Fang AU - Wang F AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. FAU - Jing, Yanling AU - Jing Y AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. FAU - Huang, Fuqiang AU - Huang F AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. FAU - Jin, Di AU - Jin D AD - Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China. FAU - Wang, Ling AU - Wang L AD - First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China. Electronic address: lingwang2006@hotmail.com. FAU - Zhang, Hongbing AU - Zhang H AD - State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China; Department of Neurology, Institute of Neural Regeneration and Repair, The First People's Hospital of Yichang, College of Medicine, Three Gorges University, Yichang, 443000, China. Electronic address: hbzhang@ibms.pumc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190518 PL - China TA - J Genet Genomics JT - Journal of genetics and genomics = Yi chuan xue bao JID - 101304616 RN - 0 (GOLM1 protein, human) RN - 0 (MIRN145 microRNA, human) RN - 0 (Membrane Proteins) RN - 0 (MicroRNAs) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Carcinogenesis/genetics MH - Carcinoma, Hepatocellular/*pathology MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Exosomes/metabolism MH - Glycogen Synthase Kinase 3 beta/*metabolism MH - Hep G2 Cells MH - Humans MH - Liver Neoplasms/*pathology MH - Matrix Metalloproteinases/*metabolism MH - Membrane Proteins/*metabolism MH - MicroRNAs/*genetics MH - Neoplasm Invasiveness/genetics MH - Neoplasm Metastasis/genetics MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Exosome OT - GOLM1 OT - Hepatocellular carcinoma OT - mTOR OT - miR-145 EDAT- 2019/06/13 06:00 MHDA- 2020/06/23 06:00 CRDT- 2019/06/13 06:00 PHST- 2018/10/12 00:00 [received] PHST- 2019/03/06 00:00 [revised] PHST- 2019/03/06 00:00 [accepted] PHST- 2019/06/13 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/06/13 06:00 [entrez] AID - S1673-8527(19)30085-2 [pii] AID - 10.1016/j.jgg.2019.03.013 [doi] PST - ppublish SO - J Genet Genomics. 2019 May 20;46(5):235-245. doi: 10.1016/j.jgg.2019.03.013. Epub 2019 May 18.