Identification of MT1E as a novel tumor suppressor in hepatocellular carcinoma

Background: Metallothioneins (MTs) involves in the tumorigenesis and prognosis of various cancers. The bio-logical function and methylation status of MT1E in hepatocellular carcinoma (HCC) remain to be elucidated. Methods: We analyzed differentially expressed genes (DEGs) in tumor tissue samples and normal samples from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, and identified the expression levels of MT1E in the HCC. Then, the expression levels and methylation status of MT1E in HCC tissues and cells were validated by qRT-PCR and methylation-specific PCR (MSP). Also, MTT, colony formation, transwell assays, and flow cytometry, as well as xenograft model, were used to assess the biological roles of MT1E in HCC. Results: Downregulated expression of MT1E was found in HCC tissues, and was notably correlated with an aberrant methylation level of the gene promoter. Moreover, our study verified that MT1E suppressed cell growth in vitro and vivo. Further study demonstrated that MT1E could induce apoptosis and suppress the metastasis of HCC cells. Conclusions: Our results suggested that epigenetic silencing of MT1E due to promoter hypermethylation could play a vital role in HCC.