Gene network analysis of the transcriptome impact of methylated microRNAs on oral squamous cell carcinoma

Abstract

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.Materials 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.

THE STUDY OF PROGNOSTIC VALUE OF microRNAs (miR-10b AND -155) AND CDKN2A/P16INK4A IN ORAL SQUAMOUS CELL CARCINOMA

“…Several recent studies highlight the importance of another epigenetic mechanism of gene expression regulation, namely DNA methyla-tion. Avram et al [21] evaluated the impact of the differentially methylated microRNAs in the OSCC transcriptome. They concluded that in contrast to the general decrease in DNA methylation across the entire genome in OSCC, mi-croRNA loci may exhibit an increase in their methylation status.…”

A Retrospective Analysis from Western Romania Comparing the Treatment and Survivability of p16-Positive versus p16-Negative Oropharyngeal Cancer

“…HPV’s carcinogenic potential is driven by its E6 and E7 oncoproteins [ 21 , 23 , 24 , 25 ]. These proteins provoke uncontrolled cell proliferation.…”

miR-125b-5p, miR-155-3p, and miR-214-5p and Target E2F2 Gene in Oral Squamous Cell Carcinoma

“…The action mechanism of miRNA is based on binding to the 3′-UTR of mRNAs and silencing them [ 12 , 13 ]. These types of RNA are involved in the post-transcriptional regulation of approximately 60% of human genes [ 14 ]. miRNAs play an important role in modulating processes such as embryogenesis, cellular development, cell proliferation, cell metabolism, and homeostasis [ 13 ].…”