Figure 7
From: Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities
Working model. Metformin treatment downregulated, transcriptionally, the levels of miR-21-5p by inhibiting its transcription through increased occupancy of the promoter regions by E2F3. Consequently, this relieved the mir-21-5p-mediated repression of calcium-binding protein 39-like (CAB39L) and Sestrin-1 levels. This, in turn, activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) signaling, discouraging clonogenicity and invasion of the treated cells, independently of their phosphatase and tensin homolog (PTEN) status.
