title: miR-34a repression of SIRT1 regulates apoptosis.
abstract: MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation is not completely understood. We now show that the microRNA miR-34a regulates silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through a miR-34a-binding site within the 3' UTR of SIRT1. MiR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway.
authors.affiliation: Departments of Medicine and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. myamaku1@jhmi.edu
authors.forename: Munekazu
authors.initials: M
authors.lastname: Yamakuchi
authors.forename: Marcella
authors.initials: M
authors.lastname: Ferlito
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lowenstein