The regulation of microRNA (miRNA) biogenesis and the role of miRNA binding proteins in breast cancer.

MicroRNAs是一类新发现的分子，在细胞内起到遗传调节的作用。它们控制细胞分裂和细胞死亡的过程，并在预防癌症方面发挥重要作用。我们已经发现，雌激素(乳腺癌的主要调节因子)会导致特定microRNAs的产生。这些微小RNA下调雌激素受体α编码基因的活性，该受体通过刺激称为雌激素反应元件的特定蛋白质的产生，在细胞内发挥雌激素的功能。这意味着永远不会有太多的雌激素活性，而且它是在我们已经确定的一个独特的反馈循环中受到控制的。然而，在乳腺癌中，microRNAs没有正确地产生，因此雌激素活性没有下调，乳腺癌细胞继续分裂。如果我们能够关闭这一过程，或者给患者提供他们不能产生的microRNA，我们就可以治疗乳腺癌并逆转这一过程。首先，我们必须确定乳腺癌中不同类型的microRNA，并了解哪些因素控制microRNA的产生。这将为诊断和针对患者的治疗提供令人兴奋的新可能性，并可能帮助我们发现难以诊断的癌症，并确定癌症的侵袭性。

MicroRNAs are a newly discovered class of molecules that act as genetic regulators within cells. They control processes involved in cell division and cell death, and have important roles in preventing cancer. We have found that estrogen (a major regulator in breast cancer,) causes production of specific microRNAs. These microRNAs down-regulate the activity of the gene that codes for the estrogen receptor-alpha - which performs the functions of estrogen inside cells by stimulating the production of particular proteins called estrogen response elements. This means that there is never too much estrogenic activity and it is controlled, in a unique feedback loop that we have identified. In breast cancer however, the microRNAs are not properly produced, so there is no down-regulation of estrogenic activity, and the breast cancer cells continue to divide. If we can turn this process off, or give patients the microRNAs they don‘t make, we can treat breast cancer and reverse this process. Firstly, we must identify the different types of microRNAs in breast cancer and understand which factors control microRNA production. This would present exciting new possibilities for diagnosis and patient-specific treatments, and may help us to detect hard-to-diagnose cancer and determine how aggressively a cancer might behave.