Published online Aug 10, 2014. doi: 10.5306/wjco.v5.i3.323
Revised: March 31, 2014
Accepted: May 13, 2014
Published online: August 10, 2014
Processing time: 226 Days and 23.2 Hours
The control of the half-life of mRNA 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 mRNA encoding growth factors, oncogenes, cell cycle regulators and inflammatory cytokines that participate in cancer. Substantial stability means that a mRNA 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 mRNA is regulated at the 3’UTR level by different mechanisms involving mRNA binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation. All these events are tightly inter-connected to each other and lead to steady state levels of target mRNAs. Compelling evidence also suggests that both mRNA binding proteins and regulatory RNAs which participate to mRNA 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 mRNA decay and discuss the possibility of its implication in breast cancer aggressiveness and the efficacy of targeted therapy.
Core tip: This review article is dedicated to the understanding of the mechanisms involved in the regulation of mRNA half-life. mRNA relative stability is an important way to rapidly increase or decrease the level of a given gene. This process is a much more rapid mechanism compare to transcriptional regulation. Since many genes implicated in cancerous processes are regulated at the level of their half-life, the proteins and/or small non coding RNA implicated in this regulation may serve as relevant prognosis markers or predictive markers of the efficacy of chemotherapeutic agents.