Rab9a Plays An Oncogenic Role In Human Liver Cancer Cells
BIOMED RESEARCH INTERNATIONAL(2020)
Abstract
Background. RAB9, as a member of the Rab GTPase family, is required for the transport of the mannose-6-phosphate receptor (MPR) from late endosomes to trans-Golgi network (TGN). However, the role of RAB9A in tumors, including liver cancer, is still unknown. Methods. We used pcDNA3.1 plasmid to upregulate the expression of RAB9A in Hep3b cells and used specific shRNA to downregulate the expression of RAB9A in HepG2 cells. Biological functions of RAB9A were performed by CCK-8 assay, colony formation assay, apoptosis analysis, transwell assays, and wound healing assays. Finally, an in-depth mechanism study was performed by western blot. Results. RAB9A promoted the proliferation and clonality of Hep3b and HepG2 cells. RAB9A also inhibited apoptosis and the activation of mitochondrial apoptotic pathway. In addition, RAB9A promoted the invasion and migration of Hep3b and HepG2 cells. Importantly, RAB9A activated the AKT/mTOR signaling pathway in human liver cancer cells. A double-effect inhibitor (BEZ235) significantly hindered the effect of RAB9A overexpression on the proliferation and invasion of Hep3b cells. Conclusion. Our data suggest that RAB9A plays a carcinogenic role in human liver cancer progression partially through AKT signaling pathways, suggesting that RAB9A may serve as a potential therapeutic target for liver cancer therapy.
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