Polycomb group protein Suz12 is regulated by a novel miRNA-like small RNA.

Human mesenchymal stem/stromal cells (hMSCs) provide support for cancer progression, partly through their secretome that includes extracellular vesicles (EVs). Based on deep-sequencing of small RNA from EVs of MSCs, we now report the characterization of novel small RNA, named n-miR-G665, which exhibits typical properties of miRNAs. n-miR-G665 sequence is conserved and expressed in most cell types. Knockdown studies using anti-agomirs and shRNA studies demonstrated that n-miR-G665 plays an important role in cell proliferation. Functional assays to reveal the targets of n-miR-G665 showed that polycomb protein Suz12 is regulated by n-miR-G665, which in turn regulates the expression of n-miR-G665 through feedback loop mechanism. These data shed light on a previously unknown novel feedback regulatory mechanism for controlling Suz12 expression regulated by previously not described miRNA, which may highlight a new therapeutic approach to control the polycomb repressor complex 2 activity in cancers.