微小 RNA-124 通过抑制 SPRY2 和 MMP-2 促进晶状体上皮细胞凋亡。

MicroRNA-124 facilitates lens epithelial cell apoptosis by inhibiting SPRY2 and MMP-2.

机构信息

Department of Ophthalmology, The First People's Hospital of Changzhou, Changzhou, Jiangsu 223000, P.R. China.

Department of Third Institute of Clinical Medicine, Soochow University, Suzhou, Jiangsu 215006, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12020. Epub 2021 Mar 24.

Abstract

Age-related cataract (ARC) is the primary cause of blindness worldwide. Abnormal expression of microRNAs (miRNAs/miRs) has been reported to be associated with multiple diseases, including ARC. However, the potential role of miR-124 in ARC remains unclear. The present study used the human lens epithelial cell line, SRA01/04, to investigate the potential role of miR-124 in ARC. Reverse transcription-quantitative PCR analysis was performed to detect the expression levels of miR-124, protein sprouty homolog 2 (SPRY2) and matrix metalloproteinase-2 (MMP-2) in ARC tissues, while western blotting was performed to detect the protein levels of SPRY2 and MMP-2. Cell viability and apoptosis of SRA01/04 cells were assessed via Cell Counting Kit-8 and TUNEL assays, respectively. The interaction between miR-124 and SPRY2 or MMP-2 was confirmed via the dual-luciferase reporter and RNA immunoprecipitation assays. The results of the present study demonstrated that miR-124 expression was significantly upregulated in ARC tissues, and knockdown of miR-124 increased SRA01/04 cell viability and suppressed apoptosis. In addition, SPRY2 and MMP-2 expression was decreased in ARC tissues, and were demonstrated to directly bind to miR-124. Overexpression of SPRY2 or MMP-2 increased SRA01/04 cell viability and repressed apoptosis, the effects of which were reversed following overexpression of miR-124. Taken together, these results suggested that miR-124 facilitates lens epithelial cell apoptosis by modulating SPRY2 or MMP-2 expression, providing a novel treatment approach for ARC.

摘要

年龄相关性白内障 (ARC) 是全球范围内失明的主要原因。据报道,异常表达的 microRNAs (miRNAs/miRs) 与多种疾病有关,包括 ARC。然而,miR-124 在 ARC 中的潜在作用尚不清楚。本研究使用人晶状体上皮细胞系 SRA01/04 来研究 miR-124 在 ARC 中的潜在作用。通过逆转录定量 PCR 分析检测 ARC 组织中 miR-124、蛋白 sprouty 同源物 2 (SPRY2) 和基质金属蛋白酶-2 (MMP-2) 的表达水平,同时通过 Western blot 检测 SPRY2 和 MMP-2 的蛋白水平。通过 Cell Counting Kit-8 和 TUNEL 测定分别评估 SRA01/04 细胞的活力和凋亡。通过双荧光素酶报告和 RNA 免疫沉淀测定证实了 miR-124 与 SPRY2 或 MMP-2 之间的相互作用。本研究结果表明,miR-124 在 ARC 组织中表达明显上调,抑制 miR-124 可增加 SRA01/04 细胞活力并抑制凋亡。此外,SPRY2 和 MMP-2 在 ARC 组织中的表达下调,并且被证明直接与 miR-124 结合。过表达 SPRY2 或 MMP-2 可增加 SRA01/04 细胞活力并抑制凋亡,而过表达 miR-124 可逆转这些作用。总之,这些结果表明,miR-124 通过调节 SPRY2 或 MMP-2 的表达促进晶状体上皮细胞凋亡,为 ARC 提供了一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a35/7986009/8f665b73e0f0/mmr-23-05-12020-g00.jpg

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