[Cite as http://purl.org/au-research/grants/nhmrc/458649]
Prof Peter Leedman
Brief description In the past few years, an expanding number of small RNAs (ribonucleic acids) have been discovered that play a critical part in regulating multiple steps involved in the development of human tumors. One of the genes critically implicated in the development several human cancers (including breast, lung, brain, prostate and colon) is the epidermal growth factor receptor (EGFR). As a consequence, the EGFR is a key target for new biological therapies designed to reduce signaling through the EGFR pathway resulting in reduced growth. Using a computer-based algorithm, we have recently discovered that one of these small RNAs (or microRNAs) is a master regulator of EGFR levels in human breast and lung cancer. When we add the specific microRNA to cancer cells with excess EGFRs and low levels of microRNA, we can abolish EGFR expression almost completely, associated with cell death. From our studies, it appears that the level of this microRNA in tissues relates inversely to the level of EGFR. As the major site of expression of this microRNA is in the brain, we were intrigued to demonstrate that the normally high level of the microRNA is lost in brain cancers (or gliomas) which are associated with high levels of EGFR. Thus, the loss of microRNA may enable the tumor to develop, suggesting that the microRNA may act as a tumor-suppressor . In this project, we will investigate the functional role of this microRNA in a range of human tumors, determine if it can work synergistically with other new biological therapies targeting the EGFR signaling pathway, identify some of its binding partners and determine the levels of EGFR and the microRNA prospectively in a cohort of gliomas. These studies will determine the functional role of the microRNA and form the foundation for further studies to consider strategies to deliver the microRNA for therapeutics.
Funding Amount $AUD 549,196.74
Funding Scheme NHMRC Project Grants
Standard Project Grant