Transcriptome Sequencing Reveals the Mechanism behind Chemically Induced Oral Mucositis in a 3D Cell Culture Model

Area of Science:

• Oncology
• Cell Biology
• Tissue Engineering

Background:

• Oral mucositis is a frequent adverse effect of cancer therapies, particularly with mTORC1 inhibitors like everolimus.
• Current treatments for oral mucositis are often insufficient, necessitating a deeper understanding of its underlying mechanisms.

Purpose of the Study:

• To investigate the molecular mechanisms of oral mucositis induced by everolimus.
• To identify potential therapeutic targets for mitigating this side effect.

Main Methods:

• Utilized an organotypic 3D oral mucosal tissue model composed of human keratinocytes and fibroblasts.
• Treated the model with varying doses and durations of everolimus.
• Analyzed morphologic changes via microscopy and transcriptomic alterations using high-throughput RNA-Seq.

Main Results:

• Everolimus treatment led to significant alterations in key biological pathways.
• Specifically affected pathways included cornification, cytokine expression, glycolysis, and cell proliferation.
• Morphological changes were observed in the 3D oral mucosal tissue model.

Conclusions:

• The study elucidates the molecular pathways involved in everolimus-induced oral mucositis.
• Identified specific pathways provide insights into potential therapeutic targets for prevention or management.
• This research serves as a valuable resource for understanding and addressing oral mucositis.