Identification of MT1E as a novel tumor suppressor in hepatocellular carcinoma
Identification of MT1E as a novel tumor suppressor in hepatocellular carcinoma
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鉴定 MT1E 作为肝细胞癌的新型肿瘤抑制因子
DOI：
10.1016/j.prp.2020.153213
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发表时间：
2020-11-01
影响因子：
2.8
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Liu, Qichen;Lu, Feng;Chen, Zhong
背景：金属硫蛋白（MTs）参与多种癌症的发生和预后。 MT1E在肝细胞癌（HCC）中的生物学功能和甲基化状态仍有待阐明。方法：我们分析了癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库中肿瘤组织样本和正常样本中的差异表达基因（DEG），并鉴定了MT1E在HCC中的表达水平。然后，通过qRT-PCR和甲基化特异性PCR（MSP）验证HCC组织和细胞中MT1E的表达水平和甲基化状态。此外，MTT、集落形成、Transwell实验、流式细胞术以及异种移植模型也被用来评估MT1E在HCC中的生物学作用。结果：在HCC组织中发现MT1E表达下调，并且与基因启动子的异常甲基化水平显着相关。此外，我们的研究证实 MT1E 在体外和体内抑制细胞生长。进一步的研究表明MT1E可以诱导HCC细胞凋亡并抑制其转移。结论：我们的研究结果表明，由于启动子高甲基化导致的MT1E表观遗传沉默可能在HCC中发挥重要作用。
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.