Transcriptional and H3K27ac related genome profiles in oral squamous cell carcinoma cells treated with metformin.

Metformin, a first-line drug that has been used for type 2 diabetes treatment, recently attracts broad attention for its therapeutic effects on diverse human cancers. However, its effect and the underlying mechanisms on oral squamous cell carcinoma (OSCC) are not well known. OSCC cells were used to evaluate the effect of metformin on cell proliferation and colony formation . Tumor formation assay in nude mice was conducted to assess the effect of metformin . Western blotting and immunohistochemistry stain were performed to investigate the effect of metformin on the expression of acetylation at lysine 27 of histone H3 (H3K27ac) and methylation at lysine 27 of histone H3 (H3K27me3) and . RNA-seq and ChIP-seq were performed to explore the genome profile to metformin treatment in OSCC cells. Metformin inhibited OSCC cell proliferation and colony formation , as well as OSCC growth . Metformin increased the global H3K27ac modification . Transcriptome analysis suggested that metformin mainly downregulated pluripotency stem cell pathway, development involved pathways and upregulated cytokine and inflammatory pathways. Additionally, H3K27ac was involved in transcription, DNA repair and replication in metformin-treated OSCC cells. Metformin inhibits OSCC growth concomitant upregulated global level of H3K27ac . This study provides insights into the molecule and epigenome basis on application of metformin in OSCC treatment, and highlights the underlying mechanisms of reprogrammed cancer regulation and epigenetic histone modification.