The effect of extracellular vesicles derived from oral squamous cell carcinoma on the transcriptomic profile of oral fibroblasts
Oral squamous cell carcinoma (OSCC) accounts for ~90% of malignancies in the oral cavity. We have previously shown that OSCC-derived extracellular vesicles (EVs) affect the phenotype and metabolome of normal oral fibroblasts (NOFs), and that it may reflect the acquisition of a pro-tumorigenic phenotype by NOFs. The present study aimed to complement our previous findings by using high-throughput RNA-Seq and bioinformatic analysis to determine transcriptomic changes in NOFs exposed to OSCC-derived EVs.   The analyses revealed significant changes in the transcriptomic profile of NOFs in response to OSCC EVs. At 12 h following EV exposure, 423 differentially expressed genes (DEGs) were detected, and after 24 h, there were 486 DEGs. Among DEGs from the 12 and 24 h timepoints, 41.9% were common. Functional analysis showed an overwhelming number of enriched terms related to DNA replication, cell division, and the cell cycle in general, and processes associated with the cytoskeleton and migration were also enriched. The obtained results revealed that fibroblast response to OSCC EV treatment induced a detectable transcriptomic shift by 12 h, which was sustained at 24 h. The DEGs and enriched signaling pathways are of major importance for proper cell functioning of fibroblasts and suggest that OSCC EVs might cause pro-tumorigenic phenotype switch in NOFs.
Oral squamous cell carcinoma (OSCC) accounts for ~90% of malignancies in the oral cavity. We have previously shown that OSCC-derived extracellular vesicles (EVs) affect the phenotype and metabolome of normal oral fibroblasts (NOFs), and that it may reflect the acquisition of a pro-tumorigenic phenotype by NOFs. The present study aimed to complement our previous findings by using high-throughput RNA-Seq and bioinformatic analysis to determine transcriptomic changes in NOFs exposed to OSCC-derived EVs.   The analyses revealed significant changes in the transcriptomic profile of NOFs in response to OSCC EVs. At 12 h following EV exposure, 423 differentially expressed genes (DEGs) were detected, and after 24 h, there were 486 DEGs. Among DEGs from the 12 and 24 h timepoints, 41.9% were common. Functional analysis showed an overwhelming number of enriched terms related to DNA replication, cell division, and the cell cycle in general, and processes associated with the cytoskeleton and migration were also enriched. The obtained results revealed that fibroblast response to OSCC EV treatment induced a detectable transcriptomic shift by 12 h, which was sustained at 24 h. The DEGs and enriched signaling pathways are of major importance for proper cell functioning of fibroblasts and suggest that OSCC EVs might cause pro-tumorigenic phenotype switch in NOFs.
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