Promotion and suppression of hypoxic response in glioma using miRNA and miRNA inhibitor

Article information
MiR675-5p Acts on HIF-1α to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma.
Lo Dico A, Costa V, Martelli C, Diceglie C, Rajata F, Rizzo A, Mancone C, Tripodi M, Ottobrini L, Alessandro R, Conigliaro A.
Theranostics. 2016 May 8;6(8):1105-18. PMID: 27279905

Overview
In glioma, hypoxia is a driving force for tumour angiogenesis; hypoxia inducible factor-1α (HIF-1α) is thought to play an important role in regulating the vascular supply.

Also, under hypoxic conditions, HIF-1α expression is upregulated, in turn resulting in altered expression of multiple other genes, including H19. This gene, expressed as a long-chain noncoding RNA, is overexpressed in some tumours. The H19 transcript also yields miR675-5p, a miRNA that has been shown to be upregulated in glioma, gastric cancer, and colon cancer, although the role of this miRNA in the hypoxic environment has not been elucidated.

In this paper, when the authors cultured glioma cells and vascular endothelial cells under hypoxic conditions, expression of miR675-5p was elevated in both cell types.

Subsequently, the authors showed that administration of miR675-5p mimic or miR675-5p inhibitor to the co-cultured cells promoted or suppressed (respectively) the nuclear localization of HIF-1α.

In further experiments, the miR675-5p mimic or miR675-5p inhibitor was administered via the tail vein to the glioma orthotopic transplantation model using AteloGene Systemic Use. Injection of the mimic resulted in enhanced hypoxia and tumour growth, while injection of the inhibitor resulted in the suppression of hypoxia and tumour growth.

in vivo transfection reagent AteloGene

Product name
– AteloGene Systemic Use (Cat. No.: #1393 for Cosmo Bio customers)
                                            (Cat. No.: #1395 for REPROCELL customers)