Has-miR-204-5p介导椎间盘退变和相关疼痛症状的发生：来自孟德尔随机化和生物信息学的证据

Has-miR-204-5p mediates intervertebral disc degeneration and associated pain symptoms: evidence from Mendelian randomization and bioinformatics

摘要

目的 挖掘椎间盘退变 （intervertebral disc degeneration，IDD）及其相关疼痛症状的新MicroRNA生物标志物并探索相关分子机制。 方法 从已发表的文献和全基因组关联研究 （genome-wide association studies，GWAS）Catlog数据库中获取MicroRNA、背部疼痛和坐骨神经痛的GWAS数据，从基因表达综合数据库（Gene Expression Omnibus，GEO）数据库中下载IDD相关的MicroRNA和mRNA表达数据。利用孟德尔随机化和生物信息学分析挖掘关键MicroRNA，并基于GeneMANIA数据库探索其靶基因的生物学功能。 结果 孟德尔随机化分析结果表明，has-miR-204-5p与背部疼痛（GCST90018797，OR=0.9761）和坐骨神经痛（GCST90044614，OR=0.8957）均具有明显的因果效应。同时，生物信息学分析结果显示，has-miR-204-5p在IDD组织中明显低表达，其3个靶基因Ⅲ型胶原蛋白α1链（collagen type Ⅲ alpha 1 chain，COL3A1），核糖体蛋白侧柄亚基P1（ribosomal protein lateral stalk subunit P1，RPLP1）和转录因子4（transcription factor 4，TCF4）在IDD组织中异常高表达。此外，生物学功能富集分析揭示，3个靶基因主要富集在胶原蛋白、核糖体和Wnt信号通路等与IDD密切相关的生物学功能上。 结论 Has-miR-204-5p是一种可靠的IDD生物标志物，在IDD及其相关疼痛症状中发挥重要作用。

Abstract

Objective To identify novel MicroRNA biomarkers of intervertebral disc degeneration（IDD） and related pain symptoms，and to explore the underlying molecular mechanisms. Methods Genome-wide association studies（GWAS） data for MicroRNAs，back pain，and sciatica were obtained from a published article and the GWAS Catlog database. IDD-associated MicroRNA and mRNA expression data were downloaded from the GEO database. Key MicroRNAs were identified using Mendelian randomization and bioinformatics analyses. The biological functions of their target genes were explored based on the GeneMANIA database. Results Mendelian randomization analysis showed that has-miR-204-5p had significant causal effects with both back pain（GCST90018797，OR=0.9761） and sciatica（GCST90044614，OR=0.8957）. Moreover，bioinformatics analysis revealed that has-miR-204-5p was significantly less expressed in IDD tissues，and its three target genes（COL3A1，RPLP1，and TCF4） were abnormally highly expressed in IDD tissues. In addition，biological function enrichment analysis revealed that the three target genes were mainly enriched in biological functions closely related to IDD，such as collagen，ribosome，and the Wnt signaling pathway. Conclusion Has-miR-204-5p is a reliable IDD biomarker that plays an important role in IDD and associated pain symptoms.

关键词

椎间盘退变 / 孟德尔随机化 / 生物信息学 / has-miR-204-5p

Key words

intervertebral disc degeneration / Mendelian randomization / bioinformatics / has-miR-204-5p