Poster abstracts
Poster number 26 submitted by Delphine Fagegaltier
Activation of germline genes and piRNAs in cancer
Delphine Fagegaltier (Division of Genomics, Cold Spring Harbor, NY ; Department of Molecular Genetics, OSU, Columbus, OH), Norbert Perrimon (HHMI, Harvard Medical School, Department of Genetics, Boston, MA), Amanda Simcox (Department of Molecular Genetics, OSU, Columbus, OH), Gregory J Hannon (HHMI, Division of Genomics, Cold Spring Harbor, NY ; University of Cambridge, Li Ka Shing Centre, Cambridge, UK)
Abstract:
piRNAs and PIWI proteins play a major role in maintaining genome stability and cell stemness in the germline where they silence repeat-derived transcripts. In human cancers, the expression of germline genes including PIWI proteins is common. We have established a Drosophila model to investigate the role of PIWIs during cancer progression. Our study reveals oncogene and tumor suppressor alterations that can elicit the expression the piRNA pathway components in flies. In particular, we find that activated RasV12 in combination with a deficient Hippo pathway (mutant for the tumor suppressor warts, wts) is a potent inducer of ectopic expression of protein components of the piRNA machinery in cell cultures derived from fly embryos. Characterization of the cell cultures demonstrates that wts-; RasV12 cells license piRNA biogenesis and actively utilize piRNA-loaded PIWIs to modulate the expression of transposable elements and, importantly, genes relevant to cell proliferation. Together, the data provide direct evidence for a piRNA-dependent role of PIWIs in the context of somatic cancer cells. Further, the results establish that dysfunctional signaling pathways cause the piRNA-dependent machinery to regulate a network of protein coding genes, as well as non-coding RNAs, that are relevant to tumorigenesis and cancer progression.
Keywords: piRNAs, cancer, transcription