MiR675-5p Acts on HIF-1α to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma.
Hypoxia is a common feature in solid tumours. In glioma, it is considered the major driving force for tumour angiogenesis and correlates with enhanced resistance to conventional therapies, increased invasiveness and a poor prognosis for patients. Here we describe, for the first time, that miR675-5p, embedded in hypoxia-induced long non-coding RNA H19, plays a mandatory role in establishing a hypoxic response and in promoting hypoxia-mediated angiogenesis. We demonstrated, in vitro and in vivo, that miR675-5p over expression in normoxia is sufficient to induce a hypoxic moreover, miR675-5p depletion in low oxygen conditions, drastically abolishes hypoxic responses including angiogenesis. In addition, our data indicate an interaction of miR675-5p, HIF-1α mRNA and the RNA Binding Protein HuR in hypoxia-induced responses. We suggest the modulation of miR675-5p as a new therapeutic option to promote or abolish hypoxia induced angiogenesis.
1. Tecnomed Foundation of the University of Milano-Bicocca, Monza 20900, Italy; 9. Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo 90127, Italy;
Alessia
A
Lo Dico
2. Laboratory of Tissue Engineering - Innovative Technology Platforms for Tissue Engineering (PON01-00829), Rizzoli Orthopedic Institute, Palermo 90127, Italy.
Viviana
V
Costa
3. Department of Pathophysiology and Transplantation, University of Milan, Milan 20100, Italy;
Cristina
C
Martelli
3. Department of Pathophysiology and Transplantation, University of Milan, Milan 20100, Italy;; 4. Doctorate School of Molecular Medicine, University of Milan, Milan 20100, Italy;
Cecilia
C
Diceglie
5. Unità Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti "Villa Sofia-Cervello", Palermo 90100, Italy;
Francesca
F
Rajata
5. Unità Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti "Villa Sofia-Cervello", Palermo 90100, Italy;
Aroldo
A
Rizzo
6. Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza University of Rome, Rome 00185, Italy;
Carmine
C
Mancone
6. Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza University of Rome, Rome 00185, Italy;; 7. National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome 00149, Italy;
Marco
M
Tripodi
3. Department of Pathophysiology and Transplantation, University of Milan, Milan 20100, Italy;; 8. Institute of Molecular Bioimaging and Physiology (IBFM), National Researches Council (CNR), Segrate (MI) 20093, Italy;
Luisa
L
Ottobrini
9. Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo 90127, Italy;; 10. Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council of Italy, Palermo 90146, Italy.
Riccardo
R
Alessandro
6. Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza University of Rome, Rome 00185, Italy;
Alice
A
Conigliaro
D000818:Animals; D002460:Cell Line; D000067780:ELAV-Like Protein 1 / Q000378:metabolism; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology*; D064593:Heterografts; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D013312:Stress, Physiological
D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C548379:MIRN675 microRNA, human; D035683:MicroRNAs
Angiogenesis; HuR; VHL.; glioma; hypoxia; miRNA675; optical imaging