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

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

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.

Keywords: 3a and 3b; DNA methyltransferase 1; Hepatocellular carcinoma; Real time PCR; Two dimensional gel electrophoresis; Western blotting.

MeSH terms

  • Amino Acid Sequence
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / physiology*
  • DNA Methylation
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Enzyme Induction
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genotype
  • Hepacivirus / classification
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Protein Processing, Post-Translational
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Tumor Virus Infections / virology*
  • Up-Regulation

Substances

  • DNA, Neoplasm
  • DNMT3A protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human