Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, China.
Hebei International Joint Research Center for Brain Science, Shijiazhuang, 050031, China.
Curr Pharm Des. 2021;27(27):3047-3060. doi: 10.2174/1381612827666210202141541.
This study was performed to identify the alterations of Long non-coding RNAs (lncRNAs) induced by oxidative stress and investigate the functional roles of SNHG16 in the pathological angiogenesis by human retinal microvascular endothelial cells (HMRECs).
The expression profiles of lncRNAs and mRNAs induced by oxidative stress were identified by RNA-Seq, and the dysregulation of 16 lncRNAs including SNHG16 was verified in HO-treated human umbilical vein endothelial cells (HUVECs). Luciferase reporter assay and RIP analysis were used to investigate the binding relationship of SNHG16 to miR-195.
We confirmed that over-expression of SNGH16 attenuated HO-induced angiogenesis by HMRECs. In addition, SNHG16 was significantly decreased, whereas miR-195, a predictive target of SNHG16, was upregulated in HO;, HG, and AGE-treated HMRECs. The binding relationship of SNHG16 to miR-195 was subsequently verified by luciferase reporter assay and RIP analysis. SNHG16 cotransfection abolished miR-195-mediated repression on mitofusin 2 (mfn2) protein level and counteracted the inductive effect of miR-195 on angiogenesis by HMRECs.
These results indicated that decreased SNHG16 accelerates oxidative stress-induced pathological angiogenesis in HMRECs by regulating the miR-195/mfn2 axis, providing a potential target for diabetic retinopathy (DR) therapy.
本研究旨在鉴定氧化应激诱导的长非编码 RNA（lncRNA）的改变，并研究 SNHG16 在人视网膜微血管内皮细胞（HMRECs）病理性血管生成中的功能作用。
通过 RNA-Seq 鉴定氧化应激诱导的 lncRNA 和 mRNA 的表达谱，并在 HO 处理的人脐静脉内皮细胞（HUVECs）中验证包括 SNHG16 在内的 16 个 lncRNA 的失调。荧光素酶报告基因检测和 RIP 分析用于研究 SNHG16 与 miR-195 的结合关系。
我们证实，SNGH16 的过表达可减弱 HO 诱导的 HMRECs 血管生成。此外，在 HO、HG 和 AGE 处理的 HMRECs 中，SNHG16 显著下调，而 miR-195，即 SNHG16 的预测靶标，上调。荧光素酶报告基因检测和 RIP 分析随后验证了 SNHG16 与 miR-195 的结合关系。SNHG16 共转染消除了 miR-195 对线粒体融合蛋白 2（mfn2）蛋白水平的抑制作用，并拮抗了 miR-195 对 HMRECs 血管生成的诱导作用。
这些结果表明，SNHG16 的下调通过调节 miR-195/mfn2 轴加速 HMRECs 氧化应激诱导的病理性血管生成，为糖尿病视网膜病变（DR）的治疗提供了一个潜在的靶点。
