title: Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis.
abstract: Although most cancer research has focused in mRNA, non-coding RNAs are also an essential player in tumorigenesis. In addition to the well-recognized microRNAs, recent studies have also shown that epigenetic silencing by CpG island hypermethylation of other classes of non-coding RNAs, such as transcribed ultraconserved regions (T-UCRs) or small nucleolar RNAs (snoRNAs), also occur in human neoplasia. Herein we have studied the putative existence of epigenetic aberrations in the activity of PIWI proteins, an Argonaute family protein subclass, and the small regulatory PIWI-interacting RNAs (piRNAs) in testicular cancer, as the PIWI/piRNA pathway plays a critical role in male germline development. We have observed the existence of promoter CpG island hypermethylation-associated silencing of PIWIL1, PIWIL2, PIWIL4, and TDRD1 in primary seminoma and non-seminoma testicular tumors, in addition to testicular germ cell tumor cell lines. Most importantly, these epigenetic lesions occur in a context of piRNA downregulation and loss of DNA methylation of the LINE-1 repetitive sequences, one of the target genomic loci where the PIWI/piRNA machinery acts as a caretaker in non-transformed cells.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC); Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain; Programme in Experimental Biology and Biomedicine; Centre for Neurosciences and Cell Biology; University of Coimbra; Coimbra, Portugal.
authors.forename: Humberto J
authors.initials: HJ
authors.lastname: Ferreira
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC); Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
authors.forename: Holger
authors.initials: H
authors.lastname: Heyn
authors.affiliation: Medical Oncology Department; Catalan Institute of Oncology; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Garcia del Muro
authors.affiliation: Pathology Department; University Hospital Bellvitge; Bellvitge Biomedical Research Institute (IDIBEL); Barcelona, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Human Molecular Genetics Group; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Larriba
authors.affiliation: Translational Research Laboratory; Catalan Institute of Oncology; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Translational Research Laboratory; Catalan Institute of Oncology; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC); Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain; Department of Physiological Sciences II; School of Medicine; University of Barcelona; Barcelona, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA); Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008745:Methylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D060565:Argonaute Proteins; D034741:RNA, Small Interfering
keywords: DNA methylation; PIWI proteins; epigenetics; non-coding RNA; piRNAs; testicular cancer