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-1a 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.
MiR675-5p acts on HIF-1α to sustain hypoxic responses : a new therapeutic strategy for glioma / A. Lo Dico, V. Costa, C. Martelli, C. Diceglie, F. Rajata, A. Rizzo, C. Mancone, M. Tripodi, L. Ottobrini, R. Alessandro, A. Conigliaro. - In: THERANOSTICS. - ISSN 1838-7640. - 6:8(2016 May 08), pp. 1105-1118.
|Titolo:||MiR675-5p acts on HIF-1α to sustain hypoxic responses : a new therapeutic strategy for glioma|
|Parole Chiave:||angiogenesis; glioma; HuR; hypoxia; miRNA675; optical imaging; VHL; medicine (miscellaneous); pharmacology, toxicology and pharmaceutics (miscellaneous)|
|Settore Scientifico Disciplinare:||Settore MED/36 - Diagnostica per Immagini e Radioterapia|
Settore MED/50 - Scienze Tecniche Mediche Applicate
|Progetto:||Development of an integrated SPECT/MRI system for enhanced stratification of brain tumour patients prior to patient-specific radio-chemo therapy and early assessment of treatment efficacy|
|Data di pubblicazione:||8-mag-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.7150/thno.14700|
|Appare nelle tipologie:||01 - Articolo su periodico|