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|Title:||Overexpression of piRNA pathway genes in epithelial ovarian cancer|
De Arao Tan, I.
|Citation:||PLoS One, 2014; 9(6):e99687-1-e99687-11|
|Publisher:||Public Library of Science|
|Shu Ly Lim, Carmela Ricciardelli, Martin K. Oehler, Izza M. D. De Arao Tan, Darryl Russell, Frank Grützner|
|Abstract:||The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and MAEL have a repressive effect on cell invasiveness.|
|Keywords:||Ovary; Cell Line, Tumor; Humans; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Neoplasm Invasiveness; Carrier Proteins; DNA-Binding Proteins; Transcription Factors; RNA, Small Interfering; RNA, Messenger; Neoplasm Staging; In Situ Hybridization; Transfection; Signal Transduction; Gene Expression Regulation, Neoplastic; Base Sequence; Molecular Sequence Data; Adult; Aged; Aged, 80 and over; Middle Aged; Female; Argonaute Proteins; Carcinoma, Ovarian Epithelial|
|Rights:||© 2014 Lim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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