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Published on: March 30, 2019
Gene network analysis of the transcriptome impact of methylated microRNAs on oral squamous cell carcinoma
Emilia Gabriela Avram1,2, Ioana Alexandra Moatar1,3, Viktorian Miok4
1Doctoral School, Victor Babeș University of Medicine and Pharmacy, Timișoara, Romania.
Background:
Oral squamous cell carcinoma (OSCC) is one of the most common head and neck squamous cell tumors. MicroRNAs and DNA methylation, as epigenetic mechanisms, regulate the expression of oncogenes and tumor suppressor genes, contributing to the carcinogenic development. However, the current knowledge on the genetic and epigenetic landscape of OSCC is still limited.
Objectives:
To assess the transcriptomic impact of microRNAs found to be methylated through Infinium genome-wide methylation profiling of archived OSCC tissues, and to analyze their biological role using gene network analysis.
Material And Methods:
We used the Infinium array-based methylation assay to assess the genome-wide methylation status at the single-CpG-site level of DNA purified from archived OSCC tissue samples. After quality control, filtering out poorly performing probes and normalization of data, we identified the differentially methylated microRNA loci. We performed a literature-based analysis of OSCC transcriptomic data to identify the predicted target genes for each microRNA, followed by individual network and pathway enrichment analyses.
Results:
The analysis of Infinium methylation array data revealed 1469 differentially hypomethylated loci, 4 of which were of interest, namely hsa-microRNA-124-3, hsa-microRNA-24-1, hsa-microRNA-769, and hsa-microRNA-4500. Network and pathway enrichment analyses revealed multiple pathways modulated through DNA methylation-microRNA expression axes.
Conclusions:
We describe the transcriptomic impact of 4 differentially methylated microRNAs in OSCC tissues samples and discuss their role in the pathology of OSCC. These results may contribute to a better understanding of how epigenetic mechanisms such as DNA methylation and microRNAs cooperate to impact the development of OSCC.
Insights
Epigenetic regulation by DNA methylation and microRNAs impacts oral cancer. This study identified four key microRNAs involved in oral squamous cell carcinoma (OSCC) development, offering insights into cancer pathology.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent head and neck cancer.
- Epigenetic mechanisms, including microRNAs and DNA methylation, are crucial in regulating genes involved in cancer development.
- Limited understanding of the genetic and epigenetic landscape in OSCC necessitates further investigation.
Purpose of the Study:
- To investigate the transcriptomic effects of methylated microRNAs in OSCC.
- To analyze the biological functions of these microRNAs using gene network analysis.
- To elucidate the interplay between DNA methylation and microRNA expression in OSCC pathogenesis.
Main Methods:
- Genome-wide DNA methylation profiling using the Infinium array on archived OSCC tissues.
- Identification of differentially methylated microRNA loci after data quality control and normalization.
- Literature-based analysis of OSCC transcriptomic data for microRNA target gene identification, followed by network and pathway enrichment analyses.
Main Results:
- Analysis identified 1469 differentially hypomethylated loci in OSCC.
- Four microRNAs of interest were identified: hsa-microRNA-124-3, hsa-microRNA-24-1, hsa-microRNA-769, and hsa-microRNA-4500.
- Network and pathway analyses revealed multiple pathways modulated by DNA methylation-microRNA expression axes.
Conclusions:
- The study characterizes the transcriptomic impact of four differentially methylated microRNAs in OSCC.
- These findings contribute to understanding the role of epigenetic mechanisms in OSCC development.
- This research enhances comprehension of how DNA methylation and microRNAs cooperate in OSCC pathology.
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