长链非编码RNA MCM3AP-AS1在糖尿病视网膜病变中表达下调，并通过调控miR-211/SIRT1促进细胞凋亡。
LncRNA MCM3AP-AS1 is downregulated in diabetic retinopathy and promotes cell apoptosis by regulating miR-211/SIRT1.
作者信息
Xia Zhaoxia, Yang Chaoying, Yang Xiaoxi, Wu Shuduan, Feng Zhizhen, Qu Lei, Chen Xianghua, Liu Linyu, Ma Yanling
机构信息
Department of Ophthalmology, the Sixth Affiliated Hospital, Sun Yat-Sen University, No. Two Heng Road 26th, Tianhe District, Guangzhou, Guangdong, 510655, People's Republic of China.
Department of Dermatology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, People's Republic of China.
出版信息
Diabetol Metab Syndr. 2022 May 15;14(1):73. doi: 10.1186/s13098-022-00836-7.
AIM
This study aimed to investigate the role of lncRNA MCM3AP-AS1 in diabetic retinopathy (DR).
METHODS
Plasma MCM3AP-AS1 levels in DR patients (n = 80), T2DM patients (n = 80), and Controls (n = 80) were measured by qPCR and compared using ANOVA (one-way) and Tukey test. The expressions of lncRNA MCM3AP-AS1 and miR-211 in Human retinal pigment epithelial cells (hRPE) line ARPE-19 were detected by RT-qPCR. Western blot and annexin V-FITC staining were performed to investigate the role of MCM3AP-AS1/SIRT1 in ARPE-19 cell proliferation and apoptosis in vitro.
RESULTS
We observed that MCM3AP-AS1 was downregulated in DR patients 25 comparing to T2D patients without significantly complications. Bioinformatics analysis showed that MCM3AP-AS1 might bind miR-211. However, no significant correlation between these two factors was observed in DR patients. Consistently, overexpression of MCM3AP-AS1 and miR-211 failed to affect the expression of each other in hRPE. Interestingly, MCM3AP-AS1 overexpression upregulated SIRT1, a target of miR-211. Moreover, MCM3AP-AS1 was downregulated in DR patients compared to type 2 diabetic mellitus patients without significant complications. In RPEs, high glucose treatment downregulated MCM3AP-AS1. Cell apoptosis analysis showed that MCM3AP-AS1 and SIRT1 overexpression decreased the apoptotic rate of RPEs, and miR-211 overexpression reduced the effect of MCM3AP-AS1 and SIRT1 overexpression.
CONCLUSION
MCM3AP-AS1 is downregulated in DR and promotes cell apoptosis by regulating miR-211/SIRT1.
目的
本研究旨在探讨长链非编码RNA MCM3AP-AS1在糖尿病视网膜病变（DR）中的作用。
方法
采用qPCR检测糖尿病视网膜病变患者（n = 80）、2型糖尿病患者（n = 80）和对照组（n = 80）血浆中MCM3AP-AS1水平，并使用方差分析（单向）和Tukey检验进行比较。通过RT-qPCR检测人视网膜色素上皮细胞（hRPE）系ARPE-19中长链非编码RNA MCM3AP-AS1和miR-211的表达。进行蛋白质免疫印迹和膜联蛋白V-FITC染色，以研究MCM3AP-AS1/SIRT1在体外ARPE-19细胞增殖和凋亡中的作用。
结果
我们观察到，与无明显并发症的2型糖尿病患者相比，糖尿病视网膜病变患者的MCM3AP-AS1表达下调。生物信息学分析表明，MCM3AP-AS1可能与miR-211结合。然而，在糖尿病视网膜病变患者中未观察到这两个因素之间的显著相关性。同样，在hRPE中，MCM3AP-AS1和miR-211的过表达均未能影响彼此的表达。有趣的是，MCM3AP-AS1过表达上调了miR-211的靶标SIRT1。此外，与无明显并发症的2型糖尿病患者相比，糖尿病视网膜病变患者的MCM3AP-AS1表达下调。在视网膜色素上皮细胞中，高糖处理下调了MCM3AP-AS1。细胞凋亡分析表明，MCM3AP-AS1和SIRT1过表达降低了视网膜色素上皮细胞的凋亡率，而miR-211过表达则降低了MCM3AP-AS1和SIRT1过表达的作用。
结论
MCM3AP-AS1在糖尿病视网膜病变中表达下调，并通过调节miR-211/SIRT1促进细胞凋亡。
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