PHD Student at Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.
Mol Cell Biochem. 2023 Jul;478(7):1427-1438. doi: 10.1007/s11010-022-04599-7. Epub 2022 Nov 8.
Psoriasis is a persistent, inflammatory, autoimmune skin disorder which can be elicited by genetic and environmental factors. Several microRNAs (miRNAs) that are abnormally expressed in psoriasis have emerged as an interesting candidate in psoriasis pathogenesis. However, the expression profile and function of miRNA-559, and its direct target metadherin (MTDH), in psoriasis need to be further illuminated. This study intended to assess miRNA-559 and MTDH levels in skin and sera of psoriatic patients and to investigate their clinical significance in an attempt for developing novel distinct tools for early diagnosis of psoriasis. Moreover, this study aimed at exploring participation of miRNA-559 in regulating MTDH/PTEN/AKT pathway in psoriasis. Expression levels of miRNA-559, AKT, FOXO1 and PTEN were measured by real-time qRT-PCR, whereas MTDH and p27 levels were assessed by ELISA in lesional, non-lesional tissues and serum of 20 psoriatic patients and 20 matching controls. Correlation study was conducted between different parameters. The diagnostic performance of miRNA-559 and MTDH in psoriasis was estimated by receiver operating characteristic (ROC) curve analysis. Expression of miRNA-559 in psoriatic patients was significantly downregulated in both lesional tissues and serum as compared to controls. Conversely, MTDH protein level showed significant increase in both tissues and serum of psoriatic patients and was inversely correlated with miRNA-559 level. Meanwhile, levels of PTEN, AKT and FOXO1 were dramatically changed in psoriatic patients compared to controls. Furthermore, serum miRNA-559 and MTDH displayed comparable diagnostic accuracy in discriminating psoriatic patients from controls. Yet, miRNA-559 demonstrated superior diagnostic performance than MTDH in psoriasis diagnosis. Together, the current findings provide the first suggestion of a new mechanism by which downregulation of miRNA-559 might induce proliferation in psoriasis through modulating PTEN/AKT/FOXO1 pathway by positive regulation of MTDH. Thus, miRNA-559 and MTDH might be proposed as promising diagnostic biomarkers of psoriasis.
银屑病是一种持续的、炎症性的、自身免疫性皮肤病，可由遗传和环境因素引起。在银屑病中异常表达的几种 microRNA（miRNA）作为银屑病发病机制中的一个有趣候选物已经出现。然而，miRNA-559 的表达谱和功能及其直接靶基因 metadherin（MTDH）在银屑病中的作用仍需要进一步阐明。本研究旨在评估银屑病患者皮肤和血清中 miRNA-559 和 MTDH 的水平，并探讨其在银屑病中的临床意义，以期开发用于银屑病早期诊断的新型特异工具。此外，本研究旨在探讨 miRNA-559 参与调节银屑病中 MTDH/PTEN/AKT 通路的作用。通过实时 qRT-PCR 测定了 miRNA-559、AKT、FOXO1 和 PTEN 的表达水平，通过 ELISA 测定了 MTDH 和 p27 的水平，检测了 20 例银屑病患者和 20 例匹配对照的皮损、非皮损组织和血清。对不同参数进行了相关性研究。通过受试者工作特征（ROC）曲线分析评估了 miRNA-559 和 MTDH 在银屑病中的诊断性能。与对照组相比，银屑病患者皮损组织和血清中 miRNA-559 的表达均显著下调。相反，MTDH 蛋白水平在银屑病患者的组织和血清中均显著升高，且与 miRNA-559 水平呈负相关。同时，与对照组相比，PTEN、AKT 和 FOXO1 的水平在银屑病患者中发生了显著变化。此外，血清 miRNA-559 和 MTDH 在区分银屑病患者和对照组方面具有相当的诊断准确性。然而，miRNA-559 在银屑病诊断中的诊断性能优于 MTDH。总之，这些发现首次提出了一种新的机制，即通过正调控 MTDH 来调节 PTEN/AKT/FOXO1 通路，下调 miRNA-559 可能通过调节 MTDH 诱导银屑病细胞增殖。因此，miRNA-559 和 MTDH 可能作为银屑病有前途的诊断生物标志物。
