Exploring Long Non-Coding RNAs Associated with IP3/DAG Signaling Pathway as Potential Biomarkers Involved in Mast Cell Degranulation in Chronic Spontaneous Urticaria with 2-Year Follow-Up.
Exploring Long Non-Coding RNAs Associated with IP3/DAG Signaling Pathway as Potential Biomarkers Involved in Mast Cell Degranulation in Chronic Spontaneous Urticaria with 2-Year Follow-Up.
复制标题
探索与 IP3/DAG 信号通路相关的长非编码 RNA 作为参与慢性自发性荨麻疹肥大细胞脱颗粒的潜在生物标志物，并进行 2 年随访
DOI：
10.2147/jir.s343826
复制
发表时间：
2022
影响因子：
4.5
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Liang Y;Kong Q;Luo H;Tan J;Zhu H
目的慢性自发性荨麻疹(CSU)的发病机制涉及肌醇1，4，5-三磷酸/二酰甘油(IP3/DAG)途径引起的肥大细胞脱颗粒，但缺乏特异的生物标志物。本研究旨在研究长非编码RNA(LncRNA)的表达谱，找出与IP3/DAG通路相关的表达谱，并评价其对CSU的诊断和预后价值。方法从CSU和对照组中选取10例标本，应用基因芯片技术筛选差异表达基因(DE)。生物信息学和共表达网络分析用于鉴定与IP3/DAG途径相关的lncRNAs。用实时定量聚合酶链式反应验证LncRNA的表达水平。结合疾病特征和酶联免疫吸附试验检测的血清指标，采用Spearman分析和Logistic回归分析方法分析lncRNA相关疾病风险。应用受试者工作特征(ROC)曲线和2年随访资料评价LncRNA的诊断和预后价值。结果共鉴定出678个上调和573个下调的DE基因和609个上调和176个下调的DE mRNAs。7个lncRNAs(上调的T264761、T280622、ENST00000587970、T224062、ENST00000562459和His-1_RNA_DNA；下调的ENST00000417930)与IP3/DAG途径相关。D-二聚体和组胺水平在两组间有显著差异。相关分析表明，His-1_RNA_DNA与症状出现频率呈正相关，而His-1_RNA_DNA、ENST00000417930、T264761、T280622与最大风团直径呈负相关。回归分析显示T264761与CSU风险相关。ROC分析显示，T264761的特异性为90%，曲线下面积为0.666。在随访中，T264761低表达组的疾病控制率为82.61%。结论本研究建立了CSU中LncRNA和mRNA的表达谱，发现了与IP3/DAG通路相关的LncRNAs，该通路与CSU的发病机制有关。T264761可能是CSU的一个新的生物标志物，但其具体机制尚需进一步研究。
Purpose Chronic spontaneous urticaria (CSU) pathogenesis involves mast cell degranulation induced by the inositol 1,4,5-trisphosphate/diacylglycerol (IP3/DAG) pathway, but the condition lacks specific biomarkers. This study was performed to investigate long non-coding RNA (lncRNA) expression profiles, identify those associated with IP3/DAG pathway, and assess their diagnostic and prognostic value for CSU. Methods Ten samples were selected from CSU and control groups, and microarray was performed to screen differentially expressed (DE) lncRNAs and mRNAs. Bioinformatic and co-expression network analyses were used to identify lncRNAs associated with IP3/DAG pathway. Quantitative real-time polymerase chain reaction was used to validate lncRNA expression levels. Combined with disease characteristics and serum indices detected with enzyme-linked immunosorbent assays, Spearman analysis and logistic regression were applied to analyze lncRNA-associated disease risk. Receiver operating characteristic (ROC) curves and 2-year follow-up data were applied to evaluate lncRNA diagnostic and prognostic value. Results A total of 678 up- and 573 downregulated DE lncRNAs and 609 up- and 176 downregulated DE mRNAs were identified. Seven lncRNAs (upregulated T264761, T280622, ENST00000587970, T224062, ENST00000562459, and his-1_RNA_dna; downregulated ENST00000417930) were associated with the IP3/DAG pathway. D-dimer and histamine levels were significantly different between the two groups. Correlation analysis showed that his-1_RNA_dna positively correlated with the frequency of symptom appearance, while his-1_RNA_dna, ENST00000417930, T264761, and T280622 negatively correlated with the maximum wheal diameter. Regression analysis showed T264761 was associated with CSU risk. ROC analysis showed that the specificity of T264761 was 90%, with an area under the curve of 0.666. In follow-up, the rate of well-controlled disease in the low T264761 expression group was 82.61%. Conclusion This study established lncRNA and mRNA expression profiles in CSU and identified lncRNAs associated with IP3/DAG pathway, which is mechanistically involved in this disease. T264761 may be a novel biomarker for CSU, but further study is needed to confirm its specific mechanism.