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RAB9A Plays an Oncogenic Role in Human Liver Cancer Cells
Pengfei Sun1, Lei Li1, Zhongchao Li1
1Hepatobiliary and Pancreatic Surgery, Shandong Cancer Hospital and Institute, Shandong Fist Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Huaiyin District, Jinan City, 250117 Shandong Province, China.
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.
Insights
RAB9A promotes liver cancer growth by enhancing cell proliferation and invasion. This protein activates AKT signaling pathways, suggesting RAB9A as a potential therapeutic target for liver cancer.
Area of Science:
- Molecular Biology
- Oncology
Background:
- RAB9A, a Rab GTPase, facilitates mannose-6-phosphate receptor transport.
- The role of RAB9A in liver cancer remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of RAB9A in human liver cancer.
- To elucidate the underlying molecular mechanisms of RAB9A's role in liver cancer progression.
Main Methods:
- RAB9A expression was modulated using pcDNA3.1 plasmid and shRNA in Hep3b and HepG2 cells.
- Cell proliferation, apoptosis, invasion, and migration were assessed using CCK-8, colony formation, apoptosis analysis, transwell, and wound healing assays.
- Western blot analysis and pathway inhibition (BEZ235) were employed to study mechanisms.
Main Results:
- RAB9A overexpression enhanced proliferation, clonality, invasion, and migration in liver cancer cells.
- RAB9A inhibited apoptosis and mitochondrial apoptotic pathway activation.
- RAB9A activated the AKT/mTOR signaling pathway, and its inhibition partially reversed RAB9A's oncogenic effects.
Conclusions:
- RAB9A exhibits a carcinogenic role in human liver cancer progression.
- The AKT signaling pathway is partially involved in RAB9A-mediated liver cancer.
- RAB9A represents a potential therapeutic target for liver cancer treatment.
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