Aberrant KLK4 gene promoter hypomethylation in pediatric hepatoblastomas
Baihui Liu1, Ximao Cui1, Shan Zheng1
1Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, P.R. China.
Abstract:
DNA methylation has a crucial role in cancer biology and has been recognized as an activator of oncogenes and inactivator of tumor suppressor genes, both of which are mechanisms for tumorigenesis. Kallikrein-related peptidase 4 (KLK4), has been suggested to be an oncogene in various types of cancer. The aim of the present study was to assess the DNA methylation patterns of the KLK4 gene in cancerous samples harvested from patients with hepatoblastoma (HB). KLK4 mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction and assessed its DNA methylation patterns using high-throughput mass spectrometry on a matrix-assisted laser desorption/ionization time-of-flight mass array. A total of 10 HB and 10 normal liver tissue samples were obtained from patients with HB. The results of the present study showed that a significantly higher level of KLK4 mRNA expression levels were detected in HB tissues, as compared with the matched controls. Furthermore, the KLK4 gene promoter region was distinctively less methylated in the HB samples compared with the controls and negatively correlated with KLK4 mRNA expression levels. These findings indicate that aberrant methylation of KLK4 may contribute to its upregulated mRNA expression in HB.
Insights
Aberrant DNA methylation of the Kallikrein-related peptidase 4 (KLK4) gene is linked to hepatoblastoma (HB). Reduced KLK4 promoter methylation correlates with increased KLK4 mRNA expression in HB tissues.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- DNA methylation plays a critical role in cancer development by regulating oncogenes and tumor suppressor genes.
- Kallikrein-related peptidase 4 (KLK4) is implicated as an oncogene in several cancer types.
Purpose of the Study:
- To investigate the DNA methylation patterns of the KLK4 gene in hepatoblastoma (HB) samples.
- To determine the relationship between KLK4 gene methylation and its expression levels in HB.
Main Methods:
- Quantitative analysis of KLK4 mRNA expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
- Assessment of KLK4 gene promoter methylation using high-throughput mass spectrometry (MALDI-TOF).
- Comparison of methylation patterns and gene expression between 10 HB tissues and 10 normal liver controls.
Main Results:
- Significantly higher KLK4 mRNA expression was observed in HB tissues compared to normal controls.
- The KLK4 gene promoter region showed significantly lower methylation levels in HB samples versus controls.
- A negative correlation was found between KLK4 promoter methylation and KLK4 mRNA expression levels.
Conclusions:
- Aberrant DNA methylation of the KLK4 gene promoter may contribute to its upregulation in hepatoblastoma.
- KLK4 could serve as a potential biomarker or therapeutic target in HB.
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