Medical Genetics Unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Center of Excellence in Molecular and Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Mol Diagn Ther. 2022 Jul;26(4):451-465. doi: 10.1007/s40291-022-00598-y. Epub 2022 Jun 27.
The interaction between genes and the environment in psoriasis is firmly coupled by epigenetic modification. Epigenetic modifications are inherited variations in gene expression devoid of DNA sequence alterations. Non-coding RNAs are regarded as one of the epigenetic modifications that lead eventually to enduring heritable variations in gene expression. In the present study, we chose the lncRNA, Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) known to have a regulatory role in psoriasis and deduced its axis of lncRNA-miRNA-mRNA through an in silico data analysis. We aimed to assess the expression levels of this lncRNA-miRNA-mRNA in patients with psoriasis to elucidate their possible roles in psoriasis management.
We investigated the lncRNA-PRINS and its target microRNAs (miRNA124-3p, miRNA203a-5p, miRNA129-5p, miRNA146a-5p, miRNA9-5p) and partner genes (NPM, G1P3) expression levels in the plasma of 120 patients with psoriasis compared to 120 healthy volunteers using quantitative real-time polymerase chain reaction and correlated the results with the patients' clinicopathological data. Finally, we performed a function, disease, and pathway enrichment analysis for the LncRNA-miRNA-mRNA axis under study.
The lncRNA PRINS, G1P3, and NPM genes showed significantly under-expressed levels while all miRNAs included in the study showed significant over-expression in patients with psoriasis relative to controls. The lncRNA PRINS, G1P3, and NPM genes showed a significant direct correlation with each other and inverse significant correlations with all miRNAs under study. All the study biomarkers showed significant results for discriminating between patients with psoriasis and controls using a receiver operating curve analysis with sensitivity over 90% except for PRINS, which was 74.2%. The G1P3 gene showed a direct significant correlation with body mass index in patients with psoriasis (p = 0.009) and an inverse significant correlation with age (p = 0.034). The NPM gene showed a significant correlation with body mass index in patients with psoriasis (p = 0.002).
Based on our results, we suggest that restoring the altered PRINS-miRNA-mRNA axis gene expression levels might represent a tool to prevent psoriasis worsening, along with standard therapy. Thus, on the clinical practice level, the PRINS-miRNA-mRNA axis expression profile can be utilized in designing specific targeted therapy aimed at applying a personalized medicine approach among patients with psoriasis.
银屑病中基因与环境的相互作用被表观遗传修饰所牢固耦合。表观遗传修饰是指在不改变 DNA 序列的情况下，基因表达的可遗传变化。非编码 RNA 被认为是导致基因表达持久可遗传变化的表观遗传修饰之一。在本研究中，我们选择了已知在银屑病中具有调节作用的长链非编码 RNA 诱导的银屑病相关应激 RNA 基因（PRINS），并通过计算机数据分析推断其长链非编码 RNA-miRNA-mRNA 轴。我们旨在评估该长链非编码 RNA-miRNA-mRNA 在银屑病患者中的表达水平，以阐明其在银屑病管理中的可能作用。
我们使用定量实时聚合酶链反应（qRT-PCR）检测了 120 例银屑病患者与 120 例健康志愿者血浆中长链非编码 RNA-PRINS 及其靶微小 RNA（miRNA124-3p、miRNA203a-5p、miRNA129-5p、miRNA146a-5p、miRNA9-5p）和靶基因（NPM、G1P3）的表达水平，并将结果与患者的临床病理数据相关联。最后，我们对所研究的 LncRNA-miRNA-mRNA 轴进行了功能、疾病和途径富集分析。
PRINS、G1P3 和 NPM 基因的表达水平显著下调，而研究中包含的所有 miRNA 均在银屑病患者中显著上调。PRINS、G1P3 和 NPM 基因之间存在显著的直接相关性，与所有研究 miRNA 之间存在显著的负相关。所有研究生物标志物在使用接收器操作曲线分析时，对区分银屑病患者和对照组的灵敏度均超过 90%，除 PRINS 为 74.2%外。G1P3 基因在银屑病患者中与体重指数呈直接显著正相关（p = 0.009），与年龄呈负相关（p = 0.034）。NPM 基因在银屑病患者中与体重指数呈显著相关（p = 0.002）。
基于我们的结果，我们认为恢复 PRINS-miRNA-mRNA 轴基因表达水平的改变可能代表一种预防银屑病恶化的工具，同时结合标准治疗。因此，在临床实践水平上，可以利用 PRINS-miRNA-mRNA 轴表达谱来设计针对银屑病患者的特定靶向治疗，以实现个体化医疗的方法。
