The recent discovery of the RNA Interference (RNAi) in mammals had a major impact on biomedical research. RNAi requires the presence of small non-coding RNA (sRNA) with a greater or lesser complementarity with a single or multiple target mRNA . The combination of these sRNA, as specific guides, with a nucleoprotein complex containing Argonaute type nucleases allows the extinction of a specific gene by cleavage or inhibition of translation of the cognate target mRNA. Since then, the comprehensive study of sRNA allows the discovery of other independent mechanisms of RNAi also responsibles for the regulation of gene expression, not only at the level of mature mRNAs and therefore at post-transcriptional and cytoplasmic effects as PTGS process, but also at the transcriptional and Nuclear level as TGS mechanism, also associated with a protein of the Argonaute family. Small RNAs-Argonaute complexes are then unsuspected mechanisms of gene regulations and our projects is based their implication on physiological or pathological conditions. A better understanding of the origin of cancers will identify new therapeutic targets and effective prognostic markers.