Micromanager with a macro-role: the role of microRNA-194 in prostate cancer metastasis

The first in a series of lab notes from our awardees, discussing their own research.

Rajdeep Das, M.D. - Graduate Student, University of Adelaide - Australia

Prostate cancer (PCa) is the second most common cancer diagnosed and a leading cause of cancer related deaths in men, worldwide. While considerable advances have been made in the treatment of localised tumours that are confined to the prostate, the disease becomes incurable once it has metastasized. Metastasis is a complex process that involves the spread of tumour cells to different parts of the body from its original site. Given that more than 90% of deaths associated with PCa are caused by metastases rather than the primary tumour, identifying mechanisms that contribute to cancer spread is an urgent requirement.

Studies from different research groups have shown that abnormal behaviour of microRNAs (miRs), a unique class of small molecules that can control hundreds to thousands of genes involved in all aspect of human physiology, can be an important factor in cancer metastasis, including PCa. In a previous study from our laboratory, we identified a novel miR called miR-194 as a marker of metastasis in men with PCa. My research aims to determine the function(s) of miR-194 in PCa metastasis and also to develop strategies to block these processes. Throughout this study I have used different PCa cell line models with a range of metastatic potential. Additionally, I have performed several cutting-edge molecular biology techniques to identify genes that directly interact with miR-194 and thereby allowing miR194 to mediate its action on PCa cells. My research results thus far show that when we increase the level of miR-194 in PCa cells, these cells become more metastatic. We also found that miR-194 is mediating its action on PCa cells by directly interacting with and suppressing a gene called SOCS2, which is a tumour suppressor. Further, we found that miR194-mediated regulation of SOCS2 led to activation of an oncogene called STAT3, a critical factor in PCa cell survival and growth.

In conclusion, through my research we found that miR-194 is involved in promoting prostate cancer metastasis and it does this by suppressing a gene called SOCS2. As future work, we aim to inhibit the function of miR-194 in PCa cells and determine whether this affects metastasis in animal models. Anti-miR therapeutics is entering the clinical area. Therefore, we believe our research will provide a platform to develop novel drugs which can target miR194 and suppress PCa metastasis, thereby reducing mortality from this disease.