KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR‐1470 and epidermal growth factor receptor

基因敲除 表皮生长因子受体 细胞凋亡 癌症研究 下调和上调 小RNA 生物 受体 分子生物学 医学 化学 内科学 基因 遗传学
作者
Jun Shao,Xubin Pan,Xiaowen Yin,Guangming Fan,Cheng Tan,Yong Yao,Yu Xin,Chao Sun
出处
期刊:Journal of Cellular Physiology [Wiley]
卷期号:234 (10): 17269-17279 被引量:32
标识
DOI:10.1002/jcp.28344
摘要

Abstract Long noncoding RNAs have been reported to play important roles in the pathogenesis of diabetic retinopathy (DR), which has been considered as the most common disease leading to vision loss. However, it is still unclear whether KCNQ1 overlapping transcript 1 (KCNQ1OT1) could affect DR. In this study, regarding quantitative reverse transcription polymerase chain reaction assay, KCNQ1OT1 level was upregulated while microRNA‐1470 (miR‐1470) was decreased in DR patients and human retinal endothelial cells. High KCNQ1OT1 expression was correlated with DR stage and low visual function. Using miR‐1470 mimic or knockdown of KCNQ1OT1 could lead to the similar phenomenon; phospho‐AKT, Bax, B‐cell lymphoma 2, and cleaved poly‐ADP ribose polymerase (PARP) were regulated, while vascularization was inhibited and apoptosis was promoted. Regarding bioinformatics analysis and in vitro dual luciferase reporter assay, there should be a negative correlation between KCNQ1OT1 and miR‐1470. Additionally, mRNA of epidermal growth factor receptor (EGFR) was proved as the target of miR‐1470 and EGFR targeting by miR‐1470 initiated KCNQ1OT1 deficiency‐induced apoptosis and promoted proliferation. KCNQ1OT1 and miR‐1470 were proved to be the promoter and repressor of EGFR, respectively. The results suggested that KCNQ1OT1 could sponge miR‐1470 and further regulate EGFR in DR.
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