Diabetes is one of the most prevalent metabolic diseases in the world. This study explored the role of long non-coding RNA HEIH in regulating the development of diabetic retinopathy (DR). The expression of HEIH gene was detected in the serum of patients with DR. Subsequently, high concentrations of D-glucose (HG) were used to stimulate ARPE-19 cells to construct a cell model of DR. HEIH was overexpressed and suppressed to further investigate the effects of HEIH on HG-induced ARPE-19 cell injury. Moreover, the regulatory relationship between HEIH and miR-939 was investigated, and a target relationship between miR-939 and VEGF in ARPE-19 cells was explored. We elucidated an association between HEIH/miR-939/VEGF axis and the PI3K/AKT pathway. HEIH was highly expressed in the serum of patients with DR. Moreover, HG-induced ARPE-19 cell injury and expression of HEIH. The overexpression of HEIE aggravated HG-induced ARPE-19 cell injury by significantly inhibiting cell viability, inducing apoptosis, promoting cytochrome C release from mitochondria to cytoplasm, and enhancing the caspase-3 activity, whereas suppression of HEIE had the opposite effects. In addition, the effects of the suppression of HEIH on HG-induced ARPE-19 cell injury were markedly reversed by inhibiting miR-939. miR-939 regulated HG-induced ARPE-19 cell injury by targeting VEGF. The suppression of HEIH reversed HG-induced activation of the PI3K/AKT signaling pathway. Our findings revealed that HEIH may contribute to DR by sponging miR-939 to target VEGF expression and by regulating the activation of the PI3K/AKT pathway. Inhibition of epidermal growth factor receptor and PI3K/Akt signaling suppresses cell proliferation and survival through regulation of Stat3 activation in human cutaneous squamous cell carcinoma. HEIH/miR-939/VEGF axis may provide a novel perspective for DR therapy.
Keywords: Diabetic retinopathy; HEIH; long non-coding RNA; miR-939; vascular endothelial growth factor.
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