Loss of CircIGF1R Suppress Cardiomyocytes Proliferation by Sponging miR-362-5p

Circular RNAs (circRNAs), generally formed by back-splicing of precursor mRNA. Increasing evidence has implicated the important role of circRNA in the cardiovascular diseases. However, the role of circ-insulin-like growth factor 1 receptor (circ-IGF1R) in cardiomyocytes(CMs) proliferation remains unclear. Here, we investigated the potential role of circIGF1R in the proliferation of cardiomyocytes. We found circIGF1R expression in heart tissues and primary cardiomyocytes from adult mice were significantly decreased than that in neonatal mice at postnatal 1 day (p1). Increased circIGF1R expression was detected in the injured neonatal heart at 0.5 and 1 days post-resection (dpr). Knockdown of circIGF1R significantly decreased the proliferation of primary CMs. Combined prediction software and luciferase reporter gene analysis revealed that circIGF1R interacted with miR-362-5p. Great increase in miR-362-5p expression was detected in adult heart compared with neonatal heart. Furthermore, heart injury significantly decreased the expression of miR-362-5p in neonatal mice. Mimics of miR-362-5p treatment significantly suppressed the proliferation of primary CMs. Target prediction and qPCR validation revealed that miR-362-5p significantly inhibited the expression of Phf3 in primary CMs. In addition, decreased Phf3 expression was detected in adult hearts compared with neonatal hearts. Consistently, increased Phf3 expression was detected in injured neonatal hearts compared with sham. Knockdown of Phf3 remarkably repressed CMs proliferation. Taken together, these findings suggest that circIGF1R might contribute to cardiomyocyte proliferation by promoting Pfh3 expression through sponging miR-362-5p.