Bufu Tang
Fangming Liu
Yuting Wu
Fang Wang
Yanling Jing
Fuqiang Huang
Di Jin
Ling Wang
Hongbing Zhang
aState 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
bFirst Affiliated Hospital, Dalian Medical University, Dalian, 116011, China
cDepartment of Radiology, Lishui Hospital of Zhejiang University, Lishui, 323000, China
dDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 323000, China
eInstitute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China
fDepartment of Neurology, Institute of Neural Regeneration and Repair, The First People's Hospital of Yichang, College of Medicine, Three Gorges University, Yichang, 443000, China
More InformationCorresponding author: E-mail address:lingwang2006@hotmail.com (Ling Wang);E-mail address: hbzhang@ibms.pumc.edu.cn (Hongbing Zhang)
Received Date: 2018-10-12
Accepted Date:2019-03-06
Rev Recd Date:2019-03-06
Available Online: 2019-05-18 Publish Date:2019-05-20
Abstract
Abstract
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-3β/matrix metalloproteinases (GSK-3β/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.Keywords: GOLM1,
mTOR,
Exosome,
Hepatocellular carcinoma
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