Relevance of microRNAs in normal and malignant development, including human testicular germ cell tumours.
The dogma of genome functionality has recently been challenged by identification of non-protein-encoding RNAs, including mi(cro)RNAs. These relatively small sequences interact with mRNA and in the mammalian system, are involved in fine-tuning the process of translation. miRNAs have been found to be of crucial importance for normal development, including stem cell formation. Recent interesting fundamental observations will be discussed in this paper, as well as their impact on the genesis of human germ cell tumours (GCTs), in particular those of the adult testis, seminomas and non-seminomas (type II), and spermatocytic seminomas (type III). miRNA cluster 371-373 is specifically involved in inhibition of cellular senescence induced by oncogenic stress in the type II GCTs. This explains the unusual presence of wild type P53, characteristic of this type of solid cancer. Specific sets of differentiating miRNA were found to characterize the various differentiation lineages within the GCTs, which simulate normal embryonic development.
Looijenga
L H J
LH
Department of Pathology, Erasmus MC - University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Josephine Nefkens Institute, Rotterdam, The Netherlands. l.looijenga@erasmusmc.nl
Gillis
A J M
AJ
Stoop
H
H
Hersmus
R
R
Oosterhuis
J W
JW
D004273:DNA, Neoplasm / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D035683:MicroRNAs; D012334:RNA, Neoplasm