| 杨立平,曹亚微,王亚莉,等.let-7c-5p通过靶向 CD74基因在糖尿病视网膜病变中的致病作用[J].安徽医药,2023,27(9):1828-1832. |
| let-7c-5p通过靶向 CD74基因在糖尿病视网膜病变中的致病作用 |
| Pathogenic role of let-7c-5p in diabetic retinopathy by targeting the CD74 gene |
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| DOI：10.3969/j.issn.1009-6469.2023.09.029 |
| 中文关键词: 糖尿病视网膜病变 基因表达综合数据库 加权基因共表达网络分析( WGCNA) 微 RNA CD74 靶向抑制 |
| 英文关键词: Diabetic retinopathy Gene expression omnibus Weighted gene coexpression network analysis (WGCNA) MicroR- NA CD74 Targeted inhibition |
| 基金项目:邢台市科学技术局项目( 2019ZC331) |
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| 中文摘要: |
| 目的探索微 RNA(miRNA)let-7c-5p通过靶向 Ⅱ型穿膜蛋白 CD74基因在糖尿病视网膜病变( DR)中的作用机制。方法 2021年 8月至 2022年 3月，基于基因表达综合数据库( GEO)数据集中 43例正常对照和 80例糖尿病视网膜病变病人的 miRNA表达谱数据，通过加权基因共表达网络分析( WGCNA)获得 miRNA和核心基因，通过实时荧光定量逆转录聚合酶链反应( qRT-PCR)和双萤光素酶实验验证其调节机制。结果生物信息学分析显示 miRNA let-7c-5p与 CD74均是与 DR进展相关的核心基因。与正常培养的人类视网膜细胞( 1.01±0.02，1.00±0.01)相比，高糖处理人类视网膜细胞会显著下调 let-7c-5p的水(0.46±0.08，P<0.001)和显著上调 CD74的水平( 3.62±0.13，P<0.001)；且高糖处理的人类视网膜细胞 let-7c-5p与 CD74表达呈负相关关系( r=-0.99，P=0.012)。在 ENCORI数据库中预测到 let-7c-5p与 CD74的结合位点，且 let-7c-5p模拟物降低了细胞中 CD74-WT的相对萤光素酶活性(1.00±0.01比 0.43±0.06，P<0.001)。结论 let-7c-5p通过靶向抑制 CD74表达的减弱促进了 DR进展。现平 |
| 英文摘要: |
| Objective To explore the mechanism of action of the microRNA (miRNA) let-7c-5p in diabetic retinopathy (DR) by tar- geting the CD74 gene of the type Ⅱ periplasmic protein.Methods From August 2021 to March 2022, miRNAs and core genes wereobtained by weighted gene coexpression network analysis (WGCNA) based on miRNA expression profiling data from 43 normal controlsand 80 patients with diabetic retinopathy in the Gene Expression Omnibus (GEO) dataset. miRNAs and core genes were verified by re-al-time fluorescence quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and dual-luciferase assays to verify the regulatory mechanisms.Results Bioinformatics analysis revealed that miRNA let-7c-5p and CD74 are both core genes associated withDR progression. Compared with normal cultured human retinal cells (1.01±0.02, 1.00±0.01), high glucose treatment of human retinalcells significantly downregulated the level of let-7c-5p (0.46±0.08, P < 0.001) and significantly upregulated the level of CD74 (3.62± 0.13, P < 0.001), and high glucose-treated human retinal cells let-7c-5p showed a negative correlation with CD74 expression (r=-0.99, P = 0.012). The binding site of let-7c-5p to CD74 was predicted in the ENCORI database, and the let-7c-5p mimic decreased the rela- tive luciferase activity of CD74-WT in cells (1.00±0.01 vs. 0.43±0.06, P < 0.001).Conclusion Let-7C-5P promotes DR progression through targeted inhibition of CD74 expression |
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