Background: The specific function of pre-mRNA processing factors (Prps) in human malignancies has not been yet investigated. The aim of the present study was to determine the impacts of Prp8 in a common human malignancy, hepatocellular carcinoma (HCC).
Materials and Methods: RT-qPCR and Western blotting were performed to measure the expression levels of Prp8 in various HCC cell lines and HCC tissues. A hepatic astrocyte line was transfected with a eukaryotic expression plasmid to overexpress Prp8. In addition, the endogenous expression level of Prp8 in HCC cells was silenced using a short hairpin RNA method, and the role of Prp8 on cell proliferation and migration was examined by Cell Counting Kit-8, wound healing assay and Transwell assays following knockdown in HCC cells, and overexpression in astrocytes.
Results: Upregulation of Prp8 expression was found to be associated with poor clinical outcomes in patients with HCC. The upregulation of Prp8 promoted cell viability, metastasis and the activity of the PI3K/Akt pathway in hepatic astrocytes cells and HCC cells. Interestingly, loss of Prp8 had no obvious impact on cell viability and migration in hepatic astrocytes, but significantly inhibit the cell malignancy of HCC cells. Functionally, the inhibition of the PI3K/Akt pathway reversed the increased cell viability and migration of HCC cells induced by Prp8 via inhibiting EMT process.
Conclusion: Collectively, the present results suggested that Prp8 served as a tumor promoter in HCC by targeting and regulating the PI3K/Akt pathway.
Keywords: pre-mRNA processing factor 8, phosphatidylinositol 3-kinase, protein kinase B, hepatocellular carcinoma