Integrative Transcriptomic Network Analysis of Butyrate Treated Colorectal Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Aberrant microRNA (miRNA) expression is implicated in colorectal cancer (CRC) development.
• Butyrate, a histone deacetylase inhibitor (HDACi) from diet, exhibits anticancer effects in CRC cells.
• The impact of butyrate on miRNA expression in CRC remains largely unexplored.

Purpose of the Study:

• To investigate the complex interplay between butyrate and miRNA-mRNA interactions in CRC cells.
• To elucidate the role of specific miRNAs in mediating the anticancer effects of butyrate.
• To understand how butyrate-induced miRNA changes influence CRC cell behavior.

Main Methods:

• Systems biology approach integrating next-generation sequencing.
• Gene Ontology (GO) and pathway enrichment analyses.
• Assessment of cell proliferation, apoptosis, cell cycle, and gene expression changes following miRNA and target gene modulation.

Main Results:

• Butyrate induced differential expression of 113 miRNAs and 2447 protein-coding genes in HCT116 CRC cells.
• The cell cycle was identified as a central pathway affected by butyrate.
• Two miRNAs, miR-139 and miR-542, cooperated with butyrate to induce apoptosis and inhibit proliferation by targeting cell cycle genes like EIF4G2 and BIRC5.

Conclusions:

• The cell cycle is a critical target pathway for butyrate's anticancer effects in CRC.
• Novel roles for specific miRNAs (miR-139, miR-542) in mediating butyrate's antiproliferative and pro-apoptotic actions were identified.
• These findings highlight the significance of miRNA-mRNA interactions in the therapeutic potential of butyrate for colorectal cancer.