Analysis of circulating miRNAs identified in patients with Oral Cavity and Oropharyngeal Squamous Cell
Next-generation sequencing. Circulating miRNAs. Liquid biopsy. Oral and oropharyngeal Squamous Cell Carcinoma. Bioinformatics analysis.
Background Recently, next-generation sequencing (NGS) technology is revolutionizing
studies on circulating miRNAs in cancer, as it enables global analysis of these small non-
coding RNAs in body fluids, allowing both the detection of those with low expression
and new ones. In this study, we identified circulating miRNAs associated with oral cavity
and oropharyngeal SCC, and further investigated their expression levels in silico,
predicted their target genes, and identified the biological pathways they regulate.
Results The RNA-seq technique was applied to plasma samples for total miRNAs
identification. The bioinformatic analyses enabled the identification of six prominent
miRNAs significantly involved with oral cavity and oropharyngeal squamous cell
carcinoma (SCC): miR-30d-5p, miR-122-5p, miR-126-3p, miR-150-5p, miR-191-5p and
miR-223-3. A total of 194 target genes, predicted for these miRNA's, common to the
TargetScan and miRDB prediction platforms, were identified. Afterwards, a functional
analysis of these genes, performed using the DAVID tool, highlighted pathways and
annotations with significant enrichment. Among them, the pathway microRNAs in
cancer, from the Kyoto Encyclopedia of Genes and Genomes (KEGG) was enriched.
From the Gene Ontology (GO), the nucleus (Cell Compartment), protein binding
(Molecular Function) and negative regulation of transcription DNA-templated
(Biological Process) annotations were enriched. In addition, the Protein-Protein
Interaction Network analysis with STRING and Cytoscape allowed the identification of
genes relevant to the studied disease: PRKCA, RRAS2, RASA1, CALML4, PAX5 and
FOXO1.
Conclusion Among the complex network of miRNAs associated with oral cavity and
oropharyngeal SCC,.our miRNoma experiment and in silico prediction of target genes,
functional analyses, and construction of the PPI network of specific miRNAs highlighted
the miR-150-5p and miR-223-3p, providing important insights into how they can
modulate the expression and function of genes in oral and oropharyngeal cancer. These
results lay the foundation for further investigations, including studies to validate the
potential of these miRNAs as diagnosis or prognosis biomarkers, or targets for the
development of novel therapeutic approaches.