SSH3 promotes malignant progression of HCC by activating FGF1-mediated FGF/FGFR pathway.

Abstract

To investigate the impact of silencing SSH3 on the expression of FGF/FGFR pathway-related genes FGF1, FGFR1, and FGFR2 in hepatocellular carcinoma (HCC) cell line, so as to further understand the role of SSH3 in proliferation and apoptosis of HCC cells. TWe first detected SSH3 expression in 51 pairs of tumor tissue specimens and adjacent tissues collected from HCC patients through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and analyzed the interplay between SSH3 expression and clinical characteristics of HCC patients. In vitro, after SSH3-silenced human HCC cell line was constructed by lentiviral transfection, Cell Counting Kit-8 (CCK-8), cell cloning assay, and flow apoptosis methods were conducted to explore the HCC cell functions. Finally, whether SSH3 exerts its biological characteristics through the FGF/FGFR pathway and the mutual regulation mechanism between SSH3 and FGF1 were further uncovered. It was found that SSH3 expression was remarkably higher in tumor tissues of HCC patients than that in normal tissues. Meanwhile, in comparison to patients with low expression of SSH3, patients with high expression of SSH3 had higher pathological grade and larger tumor size. In addition, after silencing SSH3, HCC cell proliferation ability was attenuated while the apoptosis ability was enhanced in comparison to the control group. Moreover, the protein levels of FGF1/FGFR pathway-related genes FGF1, FGFR1, and FGFR2 were markedly inhibited by the downregulation of SSH3. Meanwhile, cell recovery experiment demonstrated that the overexpression of FGF1 reversed the impact of SSH3 silencing on the proliferation and apoptosis of HCC cells. In summary, SSH3 is capable of accelerating the malignant progression of HCC by activating FGF1-mediated FGF/FGFR pathway, thus becoming a new molecular target for HCC therapy.