Circulating microRNA203 and its target genes' role in psoriasis pathogenesis

Sally Abdallah Mostafa; Mai H S Mohammad; Walaa A Negm; Gaber El Saber Batiha; Saqer S Alotaibi; Sarah M Albogami; Michel De Waard; Noha Z Tawfik; Hoda Y Abdallah

doi:10.3389/fmed.2022.988962

Circulating microRNA203 and its target genes' role in psoriasis pathogenesis

Front Med (Lausanne). 2022 Oct 20:9:988962. doi: 10.3389/fmed.2022.988962. eCollection 2022.

Authors

Affiliations

¹ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
² Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
³ Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
⁴ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.
⁵ Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia.
⁶ Smartox Biotechnology, Saint-Egrève, France.
⁷ L'institut du thorax, INSERM, CNRS, Nantes University, Nantes, France.
⁸ LabEx "Ion Channels, Science & Therapeutics", Université de Nice Sophia-Antipolis, Nice, France.
⁹ Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
¹⁰ Medical Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
¹¹ Center of Excellence in Molecular and Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Abstract

Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4-9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.

Keywords: IL8; MiR-203; SOCS3; SOCS6; TNF-α; TP63; miRNAs; psoriasis.