Therapeutic targeting of small non-coding RNAs in cancer

Project: Dissertation

Project Details


MicroRNAs (miRNAs) are a class of ~21 nucleotide long non-coding RNAs that fine-tune gene expression post-transcriptionally. Approximately 60% of all human miRNAs are encoded in introns of protein-coding genes, and over 80% of them are controlled by the same DNA regulatory elements as their hosts. miRNAs can have both oncogenic and tumor suppressive effects, and their expression is frequently deregulated in cancer.
In this project we will study the involvement of miRNAs in gene fusions, first in breast cancer and later expanding to all cancer types in The Cancer Genome Atlas (TCGA). We have previously reported that miRNA hosts are over-represented in gene fusions and that these events may be a way for the cancer cell to regulate miRNA expression in an unstable environment.
Previously published results have shown that the HER2-encoded miRNA mir-4728 has an oncogenic function in HER2-positive breast cancer. Targeting the HER2 protein with monoclonal antibodies such as Trastuzumab would not affect the oncogenic function of mir-4728. This miRNA is a potentially attractive therapeutic target and in this project we will examine the effects of targeting mir-4728 in conjunction with HER2, in cell lines and in vivo models.
Effective start/end date2020/03/012024/03/01