MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells

// Viviana Costa 1, * , Alessia Lo Dico 2, * , Aroldo Rizzo 3 , Francesca Rajata 3 , Marco Tripodi 4, 5 , Riccardo Alessandro 6, 7, * , Alice Conigliaro 4, * 1 Innovative Technological Platforms for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo, Italy 2 Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milano, Italy 3 Unita Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy 4 Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza University of Rome, Rome, Italy 5 National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy 6 Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo, Italy 7 Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council of Italy, Palermo, Italy * These authors contributed equally to this work Correspondence to: Alice Conigliaro, email: conigliaro@bce.uniroma1.it Riccardo Alessandro, email: riccardo.alessandro@unipa.it Keywords: miRNA675, CRC, EMT, metastasis, hypoxia Received: November 16, 2016 Accepted: December 27, 2016 Published: January 03, 2017 ABSTRACT The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1α, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1α; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis. Our results show that miR-675-5p , over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1α induced EMT. MiR-675-5p increases Snail transcription by a dual strategy: i) stabilizing the activity of the transcription factor HIF1α and ii) and inhibiting Snail’s repressor DDB2 (Damage specific DNA Binding protein 2). Moreover, transcriptional analyses on specimens from colon cancer patients confirmed, in vivo , the correlation between miR-675-5p over-expression and metastasis, thus identifying miR-675-5p as a new marker for colon cancer progression and therefore a putative target for therapeutic strategies.