FOXO3 and breast carcinoma: RNA-Seq has revealed various novel effects and therapeutic targets of metformin, such as enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in primary human fibroblasts [14], upregulation of activating transcription factor 3 (ATF3) in primary human hepatocytes [15], downregulation of cell division control protein 42 homolog (CDC42) in breast cancer cells [16], upregulation of krüppel-like factor 4 (KLF4) resulting in suppressed endothelial dysfunction [17], and even modulated alternative splicing in embryonic stem cells [18].