piRNAs were initially known to maintain fertility through silencing transposons during germ cell development. Since then, they have quickly been recognised to play important regulatory roles in various cancers. These small non-coding RNAs along with their associated pathway components (e.g. PIWIL1-4, MAELSTROM and more) are now known to function in cell adhesion, stem cell development and DNA damage repair pathways. These pathways, when deregulated, are known to contribute to the progression and metastatic potential of cancers.
Despite a rapidly growing body of literature on the effects of the piRNA pathway in cancer, much is still unknown about their mechanism of action in ovarian and prostate cancer progression. These epithelial cancers are major disease burdens and have in common hormone sensitivity and are highly prone to developing treatment resistance.
In this project, we investigate expression differences of the piRNA pathway genes in benign tissues, early and late stage tumors as well as in chemoresistant cells. Furthermore, we are investigating if changes in hormone levels can trigger differential expression of the piRNA pathway. We are also exploring their potential roles in cancer progression by investigating their effects on relevant cancer hallmarks.
Preliminary results suggest a change in expression of PIWIL2 (one of the core pathway genes) in ovarian cancer cells after screening pathway genes with different doses of follicle stimulating hormone and luteinising hormone in vitro. Our present work will assess differences in expression of piRNA pathway genes in different stages of ovarian and prostate cancer and in chemosensitive and chemoresistant cells. Ongoing studies are investigating the effects of overexpressing the piRNA pathway genes on cell motility, invasion, epithelial-mesenchymal transition and DNA damage in ovarian and prostate cancer cells.
Taken together, this work will contribute to a better understanding of the role of the piRNA pathway in ovarian and prostate cancer progression.