| Literature DB >> 25483038 |
Kotaro Kiga1, Yoko Fukuda-Yuzawa, Masanobu Tanabe, Shoji Tsuji, Chihiro Sasakawa, Taro Fukao.
Abstract
Overexpression of SIRT1 is frequently observed in various types of cancers, suggesting its potential role in malignancies. However, the molecular basis of how SIRT1 is elevated in cancer is less understood. Here we show that cancer-related SIRT1 overexpression is due to evasion of Sirt1 mRNA from repression by a group of Sirt1-targeting microRNAs (miRNAs) that might be robustly silenced in cancer. Our comprehensive library-based screening and subsequent miRNA gene profiling revealed a housekeeping gene-like broad expression pattern and strong CpG island-association of the Sirt1-targeting miRNA genes. This suggests aberrant CpG DNA methylation as the mechanistic background for malignant SIRT1 elevation. Our work also provides an example where epigenetic mechanisms cause the group-wide regulation of miRNAs sharing a common key target.Entities:
Keywords: 3′UTR, 3′ untranslated region; 5-Aza-dC, 5-aza-2’-deoxycytidine; CGIs, CpG islands; DNA methylation; E2F1, E2F transcription factor 1; FOXO, forkhead box O; HIC1, hypermethylated in cancer 1; LXR, liver X receptor; MicroRNA; MyoD, myogenic differentiation 1; NAD, nicotinamide adenine dinucleotide; NF-κB, nuclear factor kappa-B; OVCA1, ovarian cancer-associated gene 1 protein; OVCA2, ovarian cancer-associated gene 2 protein; PARP, poly(ADP-ribose) polymerase-1; PGC-1α, peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PUMA, p53-upregulated modulator of apoptosis; SIRT1; SIRT1, sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae); SMG6, smg-6 homolog, nonsense mediated mRNA decay factor (C. elegans); Sir2, Silent information regulator 2; cancer; epigenetics; p53, protein 53; pri-miRNA, primary miRNA
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Year: 2014 PMID： 25483038 PMCID： PMC4615778 DOI： 10.4161/rna.32093
Source DB: PubMed Journal: RNA Biol ISSN： 1547-6286 Impact factor: 4.652