Aberrant DNA methylation results in altered gene expression in non-alcoholic steatohepatitis-related hepatocellular carcinomas

Journal of Cancer Research and Clinical Oncology
Ying TianYae Kanai

Abstract

The aim of this study was to investigate DNA methylation alterations in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinomas (HCCs). Genome-wide DNA methylation analysis was performed using the Infinium Human Methylation 450 K BeadChip, and levels of mRNA expression were analyzed by quantitative reverse transcription-PCR. Compared to 36 samples of normal control liver tissue (C), DNA methylation alterations were observed on 19,281 probes in 22 samples of cancerous tissue (T) obtained from patients showing histological features compatible with NASH in their non-cancerous liver tissue (N). Among those probes, 1396 were located within CpG islands or their shores and shelves, designed around the transcription start sites of 726 genes. In representative genes, such as DCAF4L2, CKLF, TRIM4, PRC1, UBE2C and TUBA1B, both DNA hypomethylation and mRNA overexpression were observed in T samples relative to C samples, and the levels of DNA methylation and mRNA expression were inversely correlated with each other. DNA hypomethylation occurred even in N samples at the precancerous NASH stage, and this was inherited by or further strengthened in T samples. DNA hypomethylation of DCAF4L2, CKLF and UBE2C was observed in both NA...Continue Reading

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Citations

Nov 5, 2020·International Journal of Molecular Sciences·Jeongeun Hyun, Youngmi Jung
Apr 29, 2021·Antioxidants & Redox Signaling·Xiaocheng Charlie DongHyeong Geug Kim
Jul 25, 2021·International Journal of Molecular Sciences·Chunye Zhang, Ming Yang
Aug 27, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xiao-Fei PengWen-Chu Ye

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Datasets Mentioned

BETA
GSE89852

Methods Mentioned

BETA
PCR
methylation profiling

Software Mentioned

Primer Designer
GEne SeT AnaLysis Toolkit
BLAST
Primer
SPSS
GenomeStudio

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