Poster Presentation 32nd Lorne Cancer 2020

piRNA pathway genes decrease ovarian cancer invasion and can be regulated by gonadotropins (#191)

Eunice Lee 1 , Noor Alia Lokman 2 , Martin Oehler 2 3 , Carmela Ricciardelli 2 , Frank Grutzner 1
  1. Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, Australia
  2. Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
  3. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

Ovarian cancer is the most lethal gynaecologic malignancy with a much lower 5-year survival rate compared to other cancers affecting women. While much of the origin and progression of ovarian cancer are still unknown, it has known sensitivity to hormones such as gonadotropins, follicle stimulating hormone (FSH) and luteinising hormone (LH). These hormones interact with cell growth and proliferation pathways and are speculated to play an important role in the development of ovarian cancer. 

The piRNA pathway is a small non-coding RNA pathway that has traditionally been linked with retrotransposon defence in the germline. However, more recently, piRNAs and its associated pathway components (eg. PIWIL1-4, MAEL etc.) have been found to be deregulated in multiple cancers including ovarian cancer. While they are known to contribute to the progression of other cancers, knowledge on their mechanism of action and effects in ovarian cancer is still largely unknown.

In this project, we investigate the effects of piRNA pathway gene overexpression on OVCAR-3 and OV-90 ovarian cancer cell motility and invasion. In addition, we investigate the response of piRNA pathway genes to gonadotropins.

Our study found an increase in motility and invasion of OVCAR-3 in vitro following overexpression of PIWIL1 and PIWIL2. Meanwhile, OV-90 did not show any significant changes. This can be explained by OV-90 being a more invasive cell line by nature as compared to OVCAR-3. Preliminary results from the gonadotropin experiment suggest increased expression of PIWIL2 (one of the core piRNA pathway genes) after treatment with gonadotropins (FSH and LH) in OV-90 cells but there was no difference in expression for PIWIL1 and MAEL. This observation suggests that gonadotropins can regulate piRNA pathway gene expression in ovarian cancer cells.

Taken together, our result in increased motility and invasion highlights the potential role of piRNA pathway genes in the progression and metastasis of ovarian cancer. Additionally, this study raises a novel possibility that the piRNA pathway is responsive to hormone treatment.