Research & Training: Breast Cancer SPORE
Developmental Research Project:
Defining Oncogene-Specific MicroRNA Signatures in Human Breast Cancer
Principal Investigators - Andrei Goga, MD, PhD
Abstract:
MicroRNAs (miRNAs) are small non-coding RNAs that may serve as both biomarkers and new therapeutic targets for human breast cancer. Increased expression of certain miRNAs in tumor cells can act oncogenically by directly inhibiting the expression of tumor suppressor genes. Oligonucleotide antagonists, called antiMirs, can be delivered systemically and can inhibit the function of microRNAs in multiple tissues including in breast tumors. Inhibition of a specific microRNA, miR-380-5p, with antiMirs can re-activate p53 expression, resulting in the death of human tumor cells and diminished in vivo tumor growth. This and other work has raised the hope that antiMirs may have utility against tumor types, such as receptor triple-negative breast cancers, against which other selective therapeutics are lacking. Unfortunately, how different oncogene signaling pathways alter the expression of specific miRNAs in human breast cancer is poorly understood. This proposal seeks to identify miRNA signatures associated with specific oncogenes in human breast cell lines. miRNAs identified from this approach will then be validated in an expanded set of human breast cell lines, with the ultimate goal of validating these signatures in primary breast tumor samples. These oncogene-specific miRNA signatures can identify new biomarkers and therapeutic targets for human breast cancer.
