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Regulation of the m RNA half-life in breast cancer

World Journal of Clinical Oncology 2014年第3期5卷 323-334页

作者： paola griseri Gilles Pagès United Orthopedic Corporation Genetica MedicaInstitute Giannina Gaslini University of Nice Sophia Antipolis Institute for Research on Cancer and Aging of Nice (IRCAN) UMR CNRS/7284 U INSERM 108106189 NiceFrance

The control of the half-life of m RNA plays a central role in normal development and in disease progression. Several pathological conditions, such as breast cancer, correlate with deregulation of the half-life of m RNA encoding growth factors, oncogenes, cell cycle regulators and inflammatory cytokines that participate in cancer. Substantial stability means that a m RNA will be available for translation for a longer time, resulting in high levels of protein gene products, which may lead to prolonged responses that subsequently result in over-production of cellular mediators that participate in cancer. The stability of these m RNA is regulated at the 3'UTR level by different mechanisms involving m RNA binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation. All these events are tightly interconnected to each other and lead to steady state levels of target m RNAs. Compelling evidence also suggests that both m RNA binding proteins and regulatory RNAswhich participate to m RNA half-life regulation may be useful prognostic markers in breast cancers, pointing to a potential therapeutic approach to treatment of patients with these tumors. In this review, we summarize the main mechanisms involved in the regulation of m RNA decay and discuss the possibility of its implication in breast cancer aggressiveness and the efficacy of targeted therapy.

关键词： mRNA stability Breast cancer RNA binding proteins MicroRNA Alternative polyadenylation

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