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Epigenetics. 2014 Jan;9(1):113-8. doi: 10.4161/epi.27237. Epub 2013 Nov 18.

Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis.

Author information

1
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.
2
Cancer Epigenetics and Biology Program (PEBC); Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
3
Medical Oncology Department; Catalan Institute of Oncology; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
4
Pathology Department; University Hospital Bellvitge; Bellvitge Biomedical Research Institute (IDIBEL); Barcelona, Spain.
5
Human Molecular Genetics Group; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
6
Translational Research Laboratory; Catalan Institute of Oncology; Bellvitge Biomedical Research Institute (IDIBELL); Barcelona, Spain.
7
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.

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.

KEYWORDS:

DNA methylation; PIWI proteins; epigenetics; non-coding RNA; piRNAs; testicular cancer

PMID:
24247010
PMCID:
PMC3928173
DOI:
10.4161/epi.27237
[Indexed for MEDLINE]
Free PMC Article
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