Moreover, Siddiqi et al. [63] demonstrated, in human sarcoma, that HIWI (PIWIL1) mediated tumorigenesis is associated with global DNA-hypermethylation and silencing of tumor suppressor genes; it is interesting to note, among them, is present SMAD3, also identified here among the molecular target of PIWIL1/piRNA complexes. This evidence concerns the gene SMAD3 and sarcoma.