Targeting MicroRNAs with Small Molecules a Novel Approach to Treating Breast Cancer

摘要

With the discovery, in the last few years, of thousands of genes that produce small non-coding RNAs transcripts with no significant open reading frame named microRNAs (miRNAs), it has become evident that the genomic complexity of the cancer cell is far greater than expected. Breast cancer (BC) is the most common cancer in women and over a third of women with BC will develop metastatic diseases. The broad goal of our research program is to develop an innovative approach of a novel microRNA-based targeted therapy in BC, on the hypothesis that small molecule inhibitors could target miRNAs and this targeting has functional consequences in malignant cells. This proposal focuses on the identification of novel small molecule inhibitors targeting miRNAs using virtual high-throughput screening (vHTS) approaches. We already accomplished the first aim, to identify in silico small molecules that target miRNA transcripts. The second aim is under development, the identification of the functional consequences of the interaction between miRNAs and small molecules in BC cells, including cell proliferation, cell death and invasion capacity. Our project already generate preliminary data useful for the basis of a new type of miRNA-based targeted therapy that will benefit BC patients mainly with metastases, by focusing now on hits that target all six proposed miRNAs. We also developed a new method to increase the amount of tested hits, namely a sensor vector for each of the miRNAs proposed to be tested that detects the amount of specific miRNA after cell treatment with the small molecule.