Inhibition of long noncoding RNA IGF2AS promotes angiogenesis in type 2 diabetes

Background: In this study, the angiogenic effect of long noncoding RNA (lncRNA), insulin growth factor 2 antisense (IGF2AS) in type 2 diabetes was evaluated. Methods: Between Wistar rat and Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, mRNA expressions of IGF2AS and IGF2 in myocardial microvascular endothelial (mMVE) cells were compared by qRT-PCR. In GK mMVE cells, IGF2AS was inhibited by siRNA. Its effects on cell proliferation and invasion were evaluated by MTT and wound-healing assays. Also, changes of IGF2, VEGF and IGF1 in siRNA-transfected GK mMVE cells were evaluated by qRT-PCR and western blot. In IGF2AS-inhibited GK mMVE cells, IGF2 was further downregulated to evaluate its role in IGF2AS-associated angiogenic regulation, using MTT, wound-healing qRT-PCR and western blot assays, respectively. Results: IGF2AS was upregulated, whereas IGF2 was downregulated, in diabetic GK mMVE cells. IGF2AS inhibition augmented proliferation and invasion in GK mMVE cells. It also upregulated IGF2 and VEGF (not IGF1) at both molecular and protein levels. Conversely, IGF2 downregulation upregulated IGF2AS and reversely inhibited angiogenic effect of IGF2AS inhibition in GK mMVE cells. It also downregulated VEGF but had no effect on IGF1. Conclusion: IGF2AS inhibition has angiogenic effect in diabetic GK mMVE cells. The functions of IGF2AS in type 2 diabetes are very likely through the inverse regulation of IGF2, but independent of IGF1. (C) 2017 Published by Elsevier Masson SAS.