Transcription factor 3 enhances hepatocellular carcinoma metastasis by upregulating MMP11

Abstract

Abstract Transcription factor 3 (TCF3) has a vital role in tumor occurrence and progression. However, the specific functions and underlying mechanisms of dysregulated TCF3 in hepatocellular carcinoma (HCC) is not thoroughly characterized. Thus, we explored the levels and roles of TCF3 in HCC samples. In addition, TCF3 knockdown and overexpression models were developed via lentiviral vectors in HCC cells. Transwell as well as in vivo metastasis experiments were performed to measure the effects of TCF3 on HCC cell metastasis. Then, reverse transcription-quantitative PCR, serial deletion, western blotting, site-directed mutagenesis, chromatin immunoprecipitation and dual-luciferase reporter assays were done to determine the involved pathomechanisms. TCF3 levels were markedly elevated in HCC samples, and correlated with poor prognosis. Besides, overexpressed TCF3 promoted HCC cell invasion as well as migration, while TCF3 knockdown repressed HCC cell growth. In addition, TCF3 mediated MMP11 expressions. MMP11 knockdown repressed TCF3-associated HCC cell migration and invasion while its overexpression attenuated the TCF3 knockdown-mediated repression of HCC growth. In human-derived HCC samples, TCF3 were positively correlated with MMP11 in expression level. Overall, these findings highlighted that TCF3 could be regarded as a prognostic biomarker and HCC metastasis regulator.