■眼动神经麻痹(ONP)起因于控制眼外肌(EOM)的中枢神经通路的原发性异常。已发现长链非编码RNA(lncRNA)与各种神经麻痹性疾病的发病机理有关。然而,关于lncRNAs在ONP中的作用知之甚少。
■我们在斜视手术期间从ONP和恒定的外斜视(CXT)患者收集内侧直肌组织,用于RNA测序分析。揭示了差异表达的mRNA和lncRNA,并将其包括在功能富集分析中。在这些差异表达的mRNAs和lncRNAs之间进行共表达分析,然后是差异表达lncRNAs的靶基因预测。此外,构建lncRNA-microRNA和lncRNA-转录因子-mRNA相互作用网络,进一步阐述ONP内侧直肌的病理变化。此外,应用RT-qPCR进一步验证重要lncRNAs和mRNAs的表达水平,通过受试者工作特征(ROC)曲线分析检查其临床意义。
■鉴定了总共618种差异表达的lncRNA和322种差异表达的mRNA。上调的mRNA与胆碱能突触传递(如CHRM3和CHRND)和细胞外基质的组分和代谢(如CHI3L1和COL19A1)显著相关,而下调的mRNA与肌纤维的组成(如MYH7和MYL3)和收缩力(如MYH7和TNNT1)显著相关。共表达分析和靶基因预测揭示了MYH7与NR_126491.1以及MYOD1与ENST00000524479之间的强相关性。此外,lncRNAs(XR_001739409.1,NR_024160.1和XR_001738373.1)和mRNAs(CDKN1A,MYOG,MYOD1MYBPH,TMEM64,STATH,和MYL3)通过RT-qPCR进行验证。ROC曲线分析显示lncRNAs(XR_001739409.1,NR_024160.1和NR_002766.2)和mRNAs(CDKN1A,MYOG,MYOD1MYBPH,TMEM64和STATH)可能是ONP的有希望的生物标志物。
■这些结果可能会阐明ONPEOM的分子生物学,以及lncRNAs和mRNAs与临床实践的可能相关性。
UNASSIGNED: Oculomotor nerve palsy (ONP) arises from primary abnormalities in the central neural pathways that control the extraocular muscles (EOMs). Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of various neuroparalytic diseases. However, little is known about the role of lncRNAs in ONP.
UNASSIGNED: We collected medial rectus muscle tissue from ONP and constant exotropia (CXT) patients during strabismus surgeries for RNA sequencing analysis. Differentially expressed mRNAs and lncRNAs were revealed and included in the functional enrichment analysis. Co-expression analysis was conducted between these differentially expressed mRNAs and lncRNAs, followed by target gene prediction of differentially expressed lncRNAs. In addition, lncRNA-microRNA and lncRNA-transcription factor-mRNA interaction networks were constructed to further elaborate the pathological changes in medial rectus muscle of ONP. Furthermore, RT-qPCR was applied to further validate the expression levels of important lncRNAs and mRNAs, whose clinical significance was examined by receiver operating characteristic (ROC) curve analysis.
UNASSIGNED: A total of 618 differentially expressed lncRNAs and 322 differentially expressed mRNAs were identified. The up-regulated mRNAs were significantly related to cholinergic synaptic transmission (such as CHRM3 and CHRND) and the components and metabolism of extracellular matrix (such as CHI3L1 and COL19A1), while the down-regulated mRNAs were significantly correlated with the composition (such as MYH7 and MYL3) and contraction force (such as MYH7 and TNNT1) of muscle fibers. Co-expression analysis and target gene prediction revealed the strong correlation between MYH7 and NR_126491.1 as well as MYOD1 and ENST00000524479. Moreover, the differential expressions of lncRNAs (XR_001739409.1, NR_024160.1 and XR_001738373.1) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, STATH, and MYL3) were validated by RT-qPCR. ROC curve analysis showed that lncRNAs (XR_001739409.1, NR_024160.1, and NR_002766.2) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, and STATH) might be promising biomarkers of ONP.
UNASSIGNED: These results may shed light on the molecular biology of EOMs of ONP, as well as the possible correlation of lncRNAs and mRNAs with clinical practice.