RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Melatonin exhibits pleiotropic anti-cancer properties.
• RNA-sequencing (RNA-Seq) in xenograft models can distinguish tumor cell vs. tumor microenvironment (TME) responses.
• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.

Purpose of the Study:

• To investigate the anti-tumor mechanisms of melatonin in a TNBC xenograft model.
• To utilize RNA-Seq to analyze transcriptomic changes in both tumor cells and the TME following melatonin treatment.
• To identify key biological pathways and genes modulated by melatonin.

Main Methods:

• A xenograft model of MDA-MB-231 TNBC in Balb/c nude mice was established.
• Mice were treated with melatonin or vehicle, and tumor growth was monitored.
• RNA-Seq was performed on tumor tissues, with data mapped to human and mouse genomes to differentiate species-specific expression.
• Differentially expressed genes and co-expression networks (WGCNA) were analyzed.

Main Results:

• Melatonin treatment significantly reduced tumor growth (p < 0.01).
• 57 differentially expressed genes were identified in the murine TME, primarily associated with immune responses.
• WGCNA identified gene clusters in both tumor cells and TME related to immune system functions.
• Upregulation of immune-related genes Tnfaip8l2 and Il1f6 in the TME was validated.

Conclusions:

• Melatonin exerts anti-tumor effects in this TNBC model.
• These effects are mediated through the modulation of the tumor microenvironment, particularly immune cell functions.
• Transcriptomic analysis provides insights into melatonin's complex mechanisms of action against cancer.