王向英,刘勇.MiR-365a-5p通过靶向FOXO1基因调控膝骨关节炎软骨细胞增殖和凋亡的机制探讨.骨科,2025,16(1): 49-56. |
MiR-365a-5p通过靶向FOXO1基因调控膝骨关节炎软骨细胞增殖和凋亡的机制探讨 |
Study on the mechanism of miR-365a-5p regulation of the proliferation and apoptosis of chondrocytes in knee osteoarthritis by targeting FOXO1 gene |
投稿时间:2024-04-12 |
DOI:10.3969/j.issn.1674-8573.2025.01.008 |
中文关键词: 膝骨关节炎 miR-365a-5p FOXO1 软骨细胞增殖 凋亡 |
英文关键词: Knee osteoarthritis miR-365a-5p FOXO1 Chondrocyte proliferation Apoptosis |
基金项目:潍坊市科技局项目(WFWSJK-2022-233) |
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中文摘要: |
目的 挖掘miR-365a-5p在促进膝骨关节炎(knee osteoarthritis,KOA)进展中的靶向基因,并研究其作用机制。方法 纳入2020年3月至2022年3月我院收治的10例KOA病人和10例健康人群,并通过qRT-PCR方法检测KOA病人和正常人软骨细胞C-28/I2中miR-365a-5p的差异表达。通过CTD和GeneCards数据库获取KOA相关的基因,并运用miRDB数据库预测miR-365a-5p的靶基因。使用Cytoscape软件的ClueGO插件进行miR-365a-5p靶向的KOA相关的基因功能富集分析。蛋白质-蛋白质相互作用构建挖掘关键基因。最后通过细胞实验进行验证。结果 miR-365a-5p在KOA病人的血清中高表达。通过公共数据库分析预测了FOXO1是miR-365a-5p的关键靶基因并与KOA相关。细胞的功能缺失实验证实miR-365a-5p的抑制能够促进KOA条件下软骨细胞的增殖并抑制凋亡。双荧光素酶报告验证了miR-365a-5p和FOXO1的靶向关系。结论 miR-365a-5p通过靶向FOXO1促进了KOA的进展。miR-365a-5p或许能成为KOA治疗的潜在靶点。 |
英文摘要: |
Objective To explore the targeted genes of miR-365a-5p in promoting the progression of knee osteoarthritis (KOA) and study its mechanism of action. Methods A total of 10 KOA patients and 10 healthy participators admitted in our hospital were included in this study from March 2020 to March 2022. The differential expression of miR-365a-5p in C-28/I2 chondrocytes of KOA patients and normal subjects were detected by qRT-PCR. The KOA related genes were retrieved from CTD and GeneCards database. Gene targets of miR-365a-5p were predicted using miRDB. The ClueGO plugin of Cytoscape software was used to perform functional enrichment analysis of KOA-related genes targeted by miR-365a-5p. The hub genes were screened by protein-protein interaction network and verified by cell experiments. Results MiR-365a-5p was overexpressed in the serum of KOA patients. FOXO1 was predicted to be a target of miR-365a-5p based on public database, which was closely related with KOA. Loss-of-function experiment determined that inhibition of miR-365a-5p promoted the proliferation and inhibited apoptosis of chondrocytes under KOA conditions. Dual-luciferase report assay verified the target interaction between miR-365a-5p and FOXO1. Conclusion MiR-365a-5p promoted KOA development and progression by targeting FOXO1. MiR-365a-5p may be a potential target for the treatment of KOA. |
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