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Suppression of GRK6 inhibits hepatocellular carcinoma progression by arresting the cell cycle
Jun Lin1, Jinluan Lin2, Xinwen Wang3
1Department of Trauma Center and Emergency Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Trauma Center and Emergency SurgeryNational Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, China.
Background:
Hepatocellular Carcinoma (HCC) is one of the most prevalent gastrointestinal malignancies worldwide. As the third leading cause of cancer-related mortality worldwide, HCC accounts for approximately 830,000 annual deaths. G protein-coupled receptor kinase 6 (GRK6) recognized as a critical protein involved in various human diseases, remains insufficiently investigated in the context of HCC.
Methods:
Bioinformatics analysis was performed to assess the expression and prognostic significance of GRK6 in HCC. Knockdown lentivirus was applied to investigate the functional role of GRK6 downregulated in HCC. Additionally, the therapeutic values of targeting GRK6 was further evaluated using a selective inhibitor (GRK6-IN-1). The effects of GRK6 modulation on cellular functions was examined through EdU, colony formation, transwell, xenograft model, flow cytometry, and western blot assays.
Results:
The bioinformatics analysis indicated that GRK6 is overexpressed in HCC tissues, and high expression of GRK6 related to lower disease specific survival (DSS), progression free interval (PFI) and overall survival (OS). Further experiment results showed that blocking GRK6 expression by lentivirus or GRK6 inhibitor (GRK6-IN-1) can suppress HCC progression via arresting the cell cycle.
Conclusion:
In conclusion, GRK6 is highly expressed in HCC, and blocking of GRK6 expression by lentivirus or GRK6 inhibitor (GRK6-IN-1) can suppress HCC progression via arresting the cell cycle. These findings suggest that GRK6 may be present as a molecular biomarker and therapeutic target in HCC.
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