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MicroRNAs, diet, and cancer: New mechanistic insights on the epigenetic actions of phytochemicals

Department of Environmental and Molecular Toxicology, and Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
Molecular Carcinogenesis (Impact Factor: 4.77). 03/2012; 51(3):213-30. DOI: 10.1002/mc.20822
Source: PubMed

ABSTRACT There is growing interest in the epigenetic mechanisms that impact human health and disease, including the role of microRNAs (miRNAs). These small (18-25 nucleotide), evolutionarily conserved, non-coding RNA molecules regulate gene expression in a post-transcriptional manner. Several well-orchestered regulatory mechanisms involving miRNAs have been identified, with the potential to target multiple signaling pathways dysregulated in cancer. Since the initial discovery of miRNAs, there has been progress towards therapeutic applications, and several natural and synthetic chemopreventive agents also have been evaluated as modulators of miRNA expression in different cancer types. This review summarizes the most up-to-date information related to miRNA biogenesis, and critically evaluates proposed miRNA regulatory mechanisms in relation to cancer signaling pathways, as well as other epigenetic modifications (DNA methylation patterns, histone marks) and their involvement in drug resistance. We also discuss the mechanisms by which dietary factors regulate miRNA expression, in the context of chemoprevention versus therapy.

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Available from: Roderick Dashwood, Aug 18, 2014
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    • "The remaining mature single-stranded miRNA determines the specificity of the RISC complex for its target mRNA by interacting with the 3 0 -untranslated region (UTR) of the transcript. RISC target recognition is primarily determined by base pairing of nucleotides in the 'seed' region and is enhanced by additional interactions in the middle of the 3 0 region [5]. How miRNAs induce translational repression or accelerate mRNA turnover remains an ongoing debate. "
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    ABSTRACT: MicroRNAs (miRNAs) represent a class of small (21-23 nucleotides) non-coding RNAs that emerged as key post-transcriptional gene regulators, implicated in numerous physiological and pathological processes. Currently, a main focus of miRNA research is related to the roles of miRNAs in cancer development. The biogenesis and modes of action of miRNAs have not been completely elucidated; however, miRNA-mediated translational repression is involved in the regulation of almost every cellular process. Thus, pathological alterations in miRNA expression signatures are commonly associated with disease development. This review specifically focuses on miRNAs in cancer, with an emphasis on their use as potential biomarkers for cancer diagnosis and prognosis. Then, we discuss the potential use of synthetic antisense or miRNA mimetic oligonucleotides and dietary agents to modulate miRNA expression for chemotherapy and chemoprevention of cancer, respectively.
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    • "An excellent example of cooperation between a dietary vitamin A-derivative targeting a nuclear receptor and the HDAC inhibitor butyrate has been described in the treatment of acute promyelocytic leukemias (Delage & Dashwood, 2008). Finally, microRNA and long ncRNA pathways also hold promise to join soon the arsenal of epigenetic combination therapies, as their target sequence specificity may bridge the gap between genetic and epigenetic changes (De Santa et al., 2010; Guil & Esteller, 2009; Gupta et al., 2010; Parasramka et al., 2011; Tsai et al., 2010). In conclusion, cancer-inflammaton studies are revealing a dazzling complexity in the mechanisms leading to dynamic alterations of the epigenome and the need of combination therapies targeting different chromatin modifiers, to reverse disease prone epigenetic alterations for chemoprevention. "
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