mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs

Xiaochen Gai; Bufu Tang; Fangming Liu; Yuting Wu; Fang Wang; Yanling Jing; Fuqiang Huang; Di Jin; Ling Wang; Hongbing Zhang

doi:10.1016/j.jgg.2019.03.013

Volume 46 Issue 5

May 2019

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Article Navigation > Journal of Genetics and Genomics > 2019 > 46(5): 235-245

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mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs

doi: 10.1016/j.jgg.2019.03.013

a
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
b
First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China
c
Department of Radiology, Lishui Hospital of Zhejiang University, Lishui, 323000, China
d
Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 323000, China
e
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, China
f
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

More Information

Corresponding 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.
- GOLM1,
- mTOR,
- Exosome,
- Hepatocellular carcinoma

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References(35)

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