Upregulation of FIGNL1 Mediated by SOX9 Promotes the Proliferation, Migration, Invasion and Cisplatin Resistance of Hepatocellular Carcinoma Cells

Abstract

Background: Fidgetin-like 1 (FIGNL1) is overexpressed in hepatocellular carcinoma (HCC), and its high expression is correlated with the poor prognosis of patients. However, the exact role of FIGNL1 in the progression of HCC remains unclear. The purpose of this research was to investigate the role of FIGNL1 in the malignant biological behaviors of HCC and its potential mechanism. Methods: In this study, the expressions of FIGNL1 and sex determining region Y (SRY)-related High Mobility Group (HMG) box-containing gene 9 (SOX9) were evaluated by quantitative Real-Time polymerase chain reaction (qRT-PCR) and western blot. JASPAR database was applied to predict the binding site between SOX9 and FIGNL1 promoter region. The proliferation, migration and invasion of Huh7 cells were detected by means of Cell Counting Kit-8 (CCK-8), colony formation assay, wound healing and transwell assays. Flow cytometry and western blot were employed to estimate cell apoptosis and cell cycle. With the application of luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay, the combination of SOX9 with FIGNL1 was verified. Results: FIGNL1 level was greatly elevated in HCC tissues (p < 0.01, p < 0.001) and cells (p < 0.01, p < 0.001). FIGNL1 knockdown suppressed Huh7 cell proliferation (p < 0.001), migration (p < 0.01) and invasion (p < 0.001) but induced cell cycle arrest (p < 0.001). Meanwhile, FIGNL1 silencing promoted cell apoptosis and repressed cisplatin resistance in Huh7 cells (p < 0.001). SOX9 expression was abundant in HCC tissues and cells (p < 0.001). SOX9 could bind to the FIGNL1 promoter and upregulate FIGNL1 expression. SOX9 elevation counteracted the impacts of FIGNL1 knockdown on Huh7 cell proliferation (p < 0.001), migration (p < 0.01), invasion (p < 0.001), apoptosis (p < 0.05, p < 0.01, p < 0.001), cell cycle arrest and cisplatin resistance (p < 0.05, p < 0.01, p < 0.001). Conclusion: In conclusion, upregulation of FIGNL1 mediated by the transcription factor SOX9 accelerated HCC cell proliferation, metastasis and cisplatin resistance but suppressed cell apoptosis and cell cycle arrest, which might shed novel insights into the targeted therapy for HCC.