SRY-Box Transcription Factor 9 (SOX9) Affects the Proliferation, Invasion and Epithelial to Mesenchymal Transition (EMT) of Intrahepatic Cholangiocarcinoma by Regulating Transforming Growth Factor β (TGFβ)/Smad Signaling

Abstract

Intrahepatic cholangiocarcinoma (ICC) develops rapidly with a high malignancy. SOX9 expression is increased in several tumors. However, its expression and role in intrahepatic cholangiocarcinoma have not yet been elucidated. Real time PCR and Western blot were done to assess SOX9 expression in tumor tissues and adjacent tissues of ICC. ICC cell line QBC939 cells were separated into control group, SOX9 overexpression group and SOX9 siRNA group followed by analysis of cell survival by MTT assay, cell migration by cell scratch assay, cell invasion by transwell chamber, E-cadherin and Vimentin level by western blot, TGFβ/Smad signaling protein level by real time PCR. SOX9 level in tumor tissues was significantly increased compared to adjacent tissues (P < 0.05) and it was associated with TNM stage, tissue type and metastasis, and survival time (P < 0.05). Transfection of pcDNA3.1-SOX9 upregulated SOX9, promoted cell proliferation, migration and invasion, downregulated E-cadherin, upregulated Vimentin, TGF-β1 and Smad4 (P < 0.05). SOX9 siRNA transfection into QBC939 cells could significantly reverse the above mentioned changes (P < 0.05). SOX9 level is increased in intrahepatic cholangiocarcinoma and targeting SOX9 can inhibit cell migration and invasion, and EMT via regulating TGFβ/Smad signaling.