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,...

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Published in:Theranostics 2016-01, Vol.6 (8), p.1105-1118
Main Authors: Lo Dico, Alessia, Costa, Viviana, Martelli, Cristina, Diceglie, Cecilia, Rajata, Francesca, Rizzo, Aroldo, Mancone, Carmine, Tripodi, Marco, Ottobrini, Luisa, Alessandro, Riccardo, Conigliaro, Alice
Format: Article
Language:English
Subjects:
Animals
Cell Line
ELAV-Like Protein 1 - metabolism
Glioma - pathology
Glioma - physiopathology
Heterografts
Humans
Hypoxia - physiopathology
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Mice
MicroRNAs - metabolism
Neovascularization, Pathologic
Research Paper
Stress, Physiological
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Summary: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.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.14700