The oncogene Mct-1 promotes progression of hepatocellular carcinoma via enhancement of Yap-mediated cell proliferation

Abstract

Malignant T-cell-amplified sequence 1 (Mct-1) has been reported as an oncogene in multiple malignant diseases. However, the function of Mct-1 in hepatocellular carcinoma (HCC) and the molecular mechanisms underlying tumor progression have not been explored. In this study, Mct-1 expression levels in HCC tissues and cells were detected by quantitative real-time PCR and western blotting. Mct-1 shRNAs and overexpression vector were transfected into HCC cells to downregulate or upregulate Mct-1 expression. In vitro and in vivo assays were performed to investigate the function of Mct-1 in cell proliferation and apoptosis. RNA sequencing analysis (RNA-seq) was performed to explore differences in gene expression when silenced Mct-1 expression. Mct-1 was upregulated in HCC specimens and cell lines, and higher expression of Mct-1 was predictive of poor survival. Overexpression of Mct-1 was shown to promote cell proliferation and repress cell apoptosis both in vitro and in vivo. The results of RNA-seq indicated that knockdown of Mct-1 suppressed Yap expression, while the results of the luciferase assay also revealed that Mct-1 increases the activity of the Yap promoter. Restoration of Yap expression in Mct-1 knockdown cells partially recovered the promotion of cell proliferation and inhibition of apoptosis. Collectively, these results indicate that Mct-1 acts as a tumor promoter gene in HCC progression by up-regulating Yap expression and, thus, could serve a novel potential diagnostic and prognostic biomarker for HCC.