1. mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs
- Author
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Xiaochen Gai, Bufu Tang, Fuqiang Huang, Ling Wang, Di Jin, Fang Wang, Fangming Liu, Yuting Wu, Yanling Jing, and Hongbing Zhang
- Subjects
Carcinoma, Hepatocellular ,Carcinogenesis ,Matrix metalloproteinase ,medicine.disease_cause ,Exosomes ,Exosome ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Genetics ,medicine ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Glycogen synthase ,Molecular Biology ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Glycogen Synthase Kinase 3 beta ,biology ,Cell growth ,TOR Serine-Threonine Kinases ,Liver Neoplasms ,Membrane Proteins ,Hep G2 Cells ,digestive system diseases ,Microvesicles ,Matrix Metalloproteinases ,MicroRNAs ,biology.protein ,Cancer research ,Signal transduction ,030217 neurology & neurosurgery - 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.
- Published
- 2018