DNA甲基转移酶1、3a和3b在丙型肝炎相关人类肝细胞癌中的表达及其临床病理关联。

DNA methyltransferase 1, 3a, and 3b expression in hepatitis C associated human hepatocellular carcinoma and their clinicopathological association.

作者信息

Siddiqui Nadir Naveed, Ul Haq Ahtesham, Siddiqui Owais Ali, Khan Rizma

机构信息

The Karachi Institute of Biotechnology and Genetic Engineering, (KIBGE), University of Karachi, Karachi, Pakistan.

Department of Biochemistry, University of Karachi-Pakistan, Karachi, Pakistan.

出版信息

Tumour Biol. 2016 Aug;37(8):10487-97. doi: 10.1007/s13277-016-4941-1. Epub 2016 Feb 5.

DOI:10.1007/s13277-016-4941-1

Abstract

Identification of biomarker will obligate a substantial influence on various cancer management and treatment. We hypothesize that genetic/proteomic and epigenetic studies should be uncovering modifications which may be independently or jointly affect the expression of the genes that are involved in the progression of liver cancer (LC). For this purpose, we examined the effect of expressional changes of DNMTs on HCV infected LC of different genotypes. We found that both mRNA and protein expression levels of DNMT1, 3a, and 3b were upregulated in genotype 1b and 3a HCV infected patients as compared to control. However, DNMT3b mRNA levels did not change in genotypes 2a, 3, and 4, but were upregulated at the protein level by genotype 1b, 2a, and 3a. Furthermore, no significant changes were observed for DNMTs investigated in sample expressing the genotypes 5 and 6. Our findings suggest that HCV at least in part by altering DNMTs expression may play a significant role in HCC progression.

摘要

生物标志物的鉴定将对各种癌症的管理和治疗产生重大影响。我们假设，基因/蛋白质组学和表观遗传学研究应揭示那些可能独立或共同影响参与肝癌（LC）进展的基因表达的修饰。为此，我们研究了DNA甲基转移酶（DNMTs）表达变化对不同基因型丙型肝炎病毒（HCV）感染的肝癌的影响。我们发现，与对照组相比，在1b型和3a型HCV感染患者中，DNMT1、3a和3b的mRNA和蛋白质表达水平均上调。然而，在2a型、3型和4型中，DNMT3b的mRNA水平没有变化，但在蛋白质水平上，1b型、2a型和3a型使其上调。此外，在表达5型和6型的样本中，所研究的DNMTs未观察到显著变化。我们的研究结果表明，HCV至少部分地通过改变DNMTs的表达可能在肝癌进展中起重要作用。