Proteins of PIWI/Argonaute protein family are evolutionarily highly conserved and play important roles in germ-line development and transposable element repression. PIWI proteins bind Piwi interacting RNAs (piRNAs) and interact with other proteins including Maelstrom (Mael). PiRNAs have been identified in mouse testis and ovary, but expression of Piwil1, Piwil4 and Mael has so far only been found in testis. The absence of an obvious phenotype in female mouse Mael knockout has further supported the view that this pathway may not be essential for ovarian development in mammals.
We investigated the evolution and expression of piRNA pathway genes in distantly related mammals and in birds. As expected Piwil and Mael orthologs are present and expressed in the amniote testis. Importantly, we found expression of Piwil2, Piwil4 and Mael in oocytes and supporting cells in human, mouse and platypus but no Piwil1 expression in mouse and chicken ovary. This suggests an evolutionarily conserved role of Piwil genes and Mael in the amniote ovary.
A growing body of evidence implicates piRNA pathway genes in cancer. We therefore investigated, if Piwil genes and Mael may play a role in ovarian cancer. Expression analysis showed significant upregulation of Piwil1 and Mael in epithelial ovarian cancer in comparison with benign tumors and normal ovary. However, for Piwil1 we found that transcripts feature deletion of exon 7 in many tumor samples. To further investigate a possible role tumor progression we measured invasiveness in vitro after overexpression of Piwil1 and Mael in ovarian cancer cell lines. This revealed a significant decrease in invasiveness in the overexpressing cells. It is possible that the piRNA pathway is activated, maybe as a result of derepression of retrotransposons, but aberrant Piwil1 transcripts produced in ovarian cancer may affect PIWIL1 function.