Methylation analysis of histone 4-related gene HIST1H4F and its effect on gene expression in bladder cancer

•The histone-related HIST1H4F gene is abnormally hypermethylated in bladder cancer samples.•We speculated that hypermethylation of HIST1H4F can be a novel candidate biomarker for early diagnosis of bladder cancer.•There was no correlation hypermethylation of HIST1H4F and gene expression at transcrip...

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Bibliographic Details
Published in:Gene 2023-05, Vol.866, p.147352-147352, Article 147352
Main Authors: Varol, Nuray, Keles, İbrahim, Yildiz, Handan, Karaosmanoglu, Cem, Karalar, Mustafa, Zengin, Kursad, Sarici, Hasmet, Tokyol, Cigdem
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - metabolism
Bladder cancer
DNA Methylation
Gene Expression
Gene Expression Regulation, Neoplastic
HIST1H4F gene
Histone 4
Histones - genetics
Histones - metabolism
Humans
RNA, Messenger - genetics
RNA, Messenger - metabolism
Urinary Bladder Neoplasms - metabolism
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Summary:•The histone-related HIST1H4F gene is abnormally hypermethylated in bladder cancer samples.•We speculated that hypermethylation of HIST1H4F can be a novel candidate biomarker for early diagnosis of bladder cancer.•There was no correlation hypermethylation of HIST1H4F and gene expression at transcriptional levels. Recently, aberrant DNA methylation of the HIST1H4F gene (encodes Histone 4 protein) has been shown in many types of cancer, which may serve as a promising biomarker for early cancer diagnosis. However, the correlation between DNA methylation of the HIST1H4F gene and its role in gene expression is unclear in bladder cancer. Therefore, the first objective of this study is to explore the DNA methylation pattern of the HIST1H4F gene and then further elucidate its effects on HIST1H4F mRNA expression in bladder cancer. To this end, the methylation pattern of the HIST1H4F gene was analyzed by pyrosequencing and the effects of the methylation profiles of this gene on HIST1H4F mRNA expression in bladder cancer were examined by qRT-PCR. Sequencing analysis revealed significantly higher methylation frequencies of the HIST1H4F gene in bladder tumor samples compared to normal samples (p  0.05). In addition, we examined the role of hypermethylation of the HIST1H4F gene on HIST1H4F mRNA expression. We found that hypermethylation of HIST1H4F in the exon have no effect HIST1H4F mRNA expression in bladder cancer (p > 0.05). We also confirmed our finding in cultured T24 cell line which HIST1H4F gene is hypermethylated. Our results suggest that hypermethylation of the HIST1H4F seems to be a promising early diagnostic biomarker in bladder cancer patients. However, further studies are needed to determine the role of HIST1H4F hypermethylation in tumorigenesis.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2023.147352