Pleural mesothelioma (PM) is a rare and highly aggressive malignancy originating from the pleural lining. Approximately 80% of cases result from the inhalation of asbestos fibers. This exposure triggers a chronic inflammatory response in the pleura, leading to tissue damage, uncontrolled cell growth and genetic mutations that promote cancer. There are three main PM histotypes, epithelioid, biphasic, and sarcomatoid. Recent studies highlight the importance of non-coding RNAs in PM, including microRNAs (miRNAs), as potential diagnostic and prognostic cancer biomarkers.

Herein, we investigated the differential expression of inflammation-related miRNAs by RT² Profiler PCR Array Human Inflammatory Response (n=84 miRNAs) in primary mesothelioma cell lines of different histotypes, epithelioid (n=2), biphasic (n=2), and sarcomatoid (n=2), and normal human mesothelial cell lines (n=2). miRNA expression analysis was analyzed using the 2–ΔΔCt method. Log2 fold change <-2/>2 was considered statistically significant. Algorithm, i.e. miRSYSTEM was used for miRNA target genes prediction using the default setting. Gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to categorize genes and identify relevant pathway.

Our results demonstrate distinct miRNA expression profiles in PM compared to control group. A total of 10/84 (12%) miRNAs were differentially expressed when comparing PM to normal cells: of these 6/10 (60%) were upregulated and 4/10 (40%) were downregulated. To determine the potential biological relevance of the differentially expressed miRNAs to PM, we predicted the target spectrum of individual deregulated miRNAs and assessed which biological pathways were enriched with their putative targets. A total of 2,201 targets were predicted for the 4 downregulated miRNAs. GO for biological process showed that regulation of transcription of cell cycle G1/S phase transition were the most enriched processes in PM cell lines. GO for molecular function exhibited that activin receptor activity, protein serine/threonine kinase activity and DNA binding were the most enriched. Moreover, GO indicated that serine/threonine protein kinase complex, activin receptor activity, nucleus and heterochromatin were the most enriched cellular component.

Our investigation highlights that inflammation-related miRNAs are differentially regulated in PM, underscoring their potential as diagnostic biomarkers and therapeutic targets. Future studies will focus on validating these miRNA signatures in a larger panel of cell lines and patient sera, and on elucidating their functional roles in PM pathogenesis.