Pubblicato su Cell Death and Differentiation uno studio frutto della collaborazione di vari ricercatori del DSV.

Il lavoro descrive l’identificazione e la caratterizzazione di nuovi micro-RNA in grado di inibire l'espressione del gene oncosoppressore DAB2IP. Tra questi, il micro-RNA miR-149-3p viene caratterizzato in modo approfondito per le sue potenzialità oncogeniche.
Lo studio rivela che oltre ad agire nelle cellule tumorali, aumentandone motilità e capacità invasiva, il miR-149-3p viene secreto e può agire sulle cellule non-tumorali del microambiente. In particolare, riducendo i livelli di DAB2IP nelle cellule endoteliali, miR-149-3p può indurre la formazione di nuovi capillari (neo-angiogenesi), favorendo la progressione tumorale e la disseminazione delle cellule cancerose.

Abstract

The tumor suppressor DAB2IP contributes to modulate the network of information established between cancer cells and tumor microenvironment. Epigenetic and post-transcriptional inactivation of this protein is commonly observed in multiple human malignancies, and can potentially favor progression of tumors driven by a variety of genetic mutations. Performing a high-throughput screening of a large collection of human microRNA mimics, we identified miR-149-3p as a negative post-transcriptional modulator of DAB2IP. By efficiently downregulating DAB2IP, this miRNA enhances cancer cell motility and invasiveness, facilitating activation of NF-kB signaling and promoting expression of pro-inflammatory and pro-angiogenic factors. In addition, we found that miR-149-3p secreted by prostate cancer cells induces DAB2IP downregulation in recipient vascular endothelial cells, stimulating their proliferation and motility, thus potentially remodeling the tumor microenvironment. Finally, we found that inhibition of endogenous miR-149-3p restores DAB2IP activity and efficiently reduces tumor growth and dissemination of malignant cells. These observations suggest that miR-149-3p can promote cancer progression via coordinated inhibition of DAB2IP in tumor cells and in stromal cells.angiogenesi), favorendo la progressione tumorale e la disseminazione delle cellule cancerose.