TC2N promotes cell proliferation and metastasis in hepatocellular carcinoma by targeting the Wnt/β-catenin signaling pathway.

Hepatocellular carcinoma (HCC), one of the most prevalent cancer types globally, has an exceedingly poor prognosis. Tandem C2 domains nuclear protein (TC2N) has been implicated in tumorigenesis and serves as an oncogene or tumor suppressor in different cancer types. Here, we explore the possible regulatory activities and molecular mechanisms of TC2N in HCC progression. TC2N expression was significantly upregulated in HCC tissues and hepatoma cell lines, and this upregulation was positively correlated with tumor progression in HCC patients. The ectopic overexpression of TC2N accelerated the proliferation, migration and invasion of HCC cells, while its knockdown showed the opposite effects. Bioinformatics analysis showed that TC2N participates in the regulation of the Wnt/β-catenin signaling pathway. Mechanistically, TC2N activated the Wnt/β-catenin signaling pathway by regulating the expression levels of β-catenin and its downstream targets MMP7, c-Myc, CyclinD1, c-Jun, AXIN2 and glutamine synthase (GS). Furthermore, deletion of β-catenin effectively neutralized the regulation of TC2N in HCC proliferation and metastasis. Overall, this study showed that TC2N promotes HCC proliferation and metastasis by activating the Wnt/β-catenin signaling pathway, indicating that TC2N might be a potential molecular target for the treatment of HCC.