Politics makes for strange bedfellows, and now it seems, so does testicular cancer. According to recent research, a trio of vastly different mechanisms all contribute to a carcinogenic epigenetic chain of events involving DNAm, retroviruses, and PIWI/piRNA machinery.

PIWI proteins are an Argonaute family protein subclass and have little RNA buddies known as small regulatory PIWI-interacting RNAs (piRNAs). Together this LINE-1 fighting duo forms a pathway for stopping retroviruses from devastating the genome during the transcriptional ‘free for all’ that is male gametogenesis. Now that we’ve got the birds and the bees out of the way, here’s what Manel Esteller and colleagues from the Bellvitge Biomedical Research Institute (in Spain) observed when they investigated the epigenetics involved:

Testicular tumors are characterized by hypermethylation in the promoters of PIWI proteins (PIWIL1, PIWIL2, PIWIL4, and TDRD1).

These “epigenetic lesions” are accompanied by a downregulation of piRNA.

Intriguingly, there is also a loss of DNA methylation in LINE-1 elements, the primary genomic target for the PIWI/piRNA machinery.

Overall, these findings appear to indicate a pretty clear cancer mechanism, where disabling hypermethylation initiates a downregulation in important ncRNA machinery, which is involved in silencing retrotransposons during male germline development. It then goes for the double by hypomethylating the imprisoning promoters of those retro-genomic pirates.

Decipher this testicular love triangle over at Epigenetics, January 2014