Clinical and Prognostic Values of DNMT3B Expression in Hepatocellular Carcinoma

Jongwan Kim, Jae-Hee Park, Jae-Ho Lee
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引用次数: 2

Abstract

De novo methylation is occurred frequently during the early embryogenesis and is faithfully copied following DNA replication at each cell cycle [1]. DNA methylation is involved in many embryonic developments, biological processes, and cell differentiation [2]. The dysregulation of DNA methyltransferases (DNMTs) and subsequent aberrant DNA methylation is a key feature of human malignancies [3,4]. DNMT1, DNMT3A, and DNMT3B are the enzymatic players of DNA methylation [1,2]. DNMT3B overexpression is frequently found in tumors, especially in 30% of breast cancers [5,6]. And it result into variation in the targeting efficiency and abnormal catalytic activity contributing to cancer development and progression. Therefore, DNMT3B may act as an oncogene, and its overexpression induces an unfavorable prognosis [3-6]. Hepatocellular carcinoma (HCC) is a majority of human cancers in worldwide, and is a leading cause of death in Korea [7,8]. Recent studies about HCC showed an alteration of DNA methylation by dysregulation of DNMT3B [9,10]. Yu et al. described that telomerase reverse transcriptase (TERT) regulates DNMT3B expression in HCC and their co-operation may predict a poorer prognosis [11]. Recent advances in genomic profiling using next-generation sequencing have made it possible to identify the genetic characteristics of cancer. Large-scale cancer genome studies such as The Cancer Genome Atlas (TCGA) used to investigate genes in different cancer types [12]. However, clinicopathopISSN 2092-8335 · eISSN 2733-5380 Keimyung Med J 2021[Epub ahead of print] https://doi.org/10.46308/kmj.2022.00045 Original Article
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DNMT3B在肝细胞癌中表达的临床及预后价值
新生甲基化经常发生在胚胎发生早期,并在每个细胞周期中忠实地复制DNA复制[1]。DNA甲基化参与了许多胚胎发育、生物过程和细胞分化[2]。DNA甲基转移酶(dnmt)的失调和随后的DNA甲基化异常是人类恶性肿瘤的一个关键特征[3,4]。DNMT1、DNMT3A和DNMT3B是DNA甲基化的酶参与者[1,2]。肿瘤中经常发现DNMT3B过表达,尤其是在30%的乳腺癌中[5,6]。它导致靶向效率的变化和催化活性的异常,从而导致癌症的发生和发展。因此,DNMT3B可能作为一种致癌基因,其过表达可导致不良预后[3-6]。肝细胞癌(HCC)是世界范围内大多数人类癌症,也是韩国的主要死亡原因[7,8]。最近关于HCC的研究表明,DNA甲基化通过DNMT3B的失调而发生改变[9,10]。Yu等研究发现,端粒酶逆转录酶(TERT)调节HCC中DNMT3B的表达,二者的协同作用可能预示较差的预后[11]。利用新一代测序技术进行基因组分析的最新进展使鉴定癌症的遗传特征成为可能。大规模的癌症基因组研究,如癌症基因组图谱(The cancer genome Atlas, TCGA),用于研究不同癌症类型的基因[12]。然而,clinicopathopISSN 2092-8335·eISSN 2733-5380 Keimyung Med J 2021[Epub预印]https://doi.org/10.46308/kmj.2022.00045原创文章
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