The role of hsa-miR-193a-5p as an important factor for control of inositol in alopecia areata

Abstract

Background: MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as therapeutic agents for targeting human disease pathways; however, there is still much to be uncovered about their mechanism of gene regulation. Alopecia areata (AA) is a commonly occurring inflammatory condition characterized by the infiltration of T cells that specifically target the anagen-stage hair follicle. The limited understanding of its precise cellular mechanism may be the reason behind the scarcity of effective treatments for AA.

Aim: The significance and function of hsa-miR-193a-5p as a genetic marker for AA and its potential influence on the advancement of the disease.

Subjects and methods: A case-control study comprised 77 individuals diagnosed with AA who were matched with 75 healthy controls. In order to measure the expression of miR-200c-3p in both groups, the real-time PCR technique was utilized. The prediction of suitable genes for hsa-miR-193a-5p, as well as the identification of pathways and gene-gene interactions, were carried out using bioinformatic tools.

Results: The levels of hsa-miR-193a-5p expression were notably elevated in AA patients in comparison to healthy controls. Our prediction suggests that the involvement of hsa-miR-193a-5p in the development of AA is significant due to its influence on the inositol phosphorylation pathway and the Phosphatidylinositol signaling system, achieved through its direct impact on the IPPK gene.

Conclusion: For the first time, our study demonstrates the significant over-expression of a new miRNA, hsa-miR-193a-5p, in the blood of AA patients compared to controls, and highlights its impact on the IPPK gene and the inositol phosphorylation and Phosphatidylinositol signaling pathways, suggesting a potential therapeutic role for hsa-miR-193a-5p in AA.

Keywords: IPPK; alopecia areata; hsa‐miR‐193a‐5p; inositol.

FIGURE 1

A summary of this study design.

FIGURE 2

The difference in hsa‐miR‐193a‐5p folding change (2‐∆∆ct) for AA patients and healthy controls.

FIGURE 3

ROC curve analysis for hsa‐miR‐193a‐5p expression.

FIGURE 4

(A) A dot‐plot was performed using Shiny GO 0.77 resource to represent the most common miRNAs interact with the selected genes in this study. (B) The interactive plot also shows the relationship between miRNAs Darker nodes are more significantly and thicker edges represent more overlapped.

FIGURE 5

A dot‐plot was performed using Shiny GO 0.77 resource to represent the outcomes of KEGG pathway enrichment analyses carried out on and its validated pathways. (A) A hierarchical clustering tree summarizes the correlation among significant pathways targeted genes identified in this study. Pathways with many shared genes are clustered together. Bigger dots indicate more significant p‐values. (B) Fold enrichment showing the percentage of genes belonging to a particular pathway. Pathways have been filtered based on the FDR cut‐off the top 10 most significant pathways are shown here.

FIGURE 6

A dot‐plot was performed using Shiny GO 0.77 resource to represent the outcomes of GO biological process enrichment analyses carried out on and its validated pathways. (A) A hierarchical clustering tree summarizes the correlation among significant pathways targeted genes identified in this study. Pathways with many shared genes are clustered together. Bigger dots indicate more significant p‐values. (B) Fold enrichment showing the percentage of genes belonging to a particular pathway. Pathways have been filtered based on the FDR cut‐off the top 10 most significant pathways are shown here.

FIGURE 7

The interactive plot also shows the relationship between enriched gene ontology and enriched pathway using ShinyGO 0.77 software. Two pathways (nodes) are connected if they share 20% (default) or more genes. Darker nodes are more significantly enriched gene sets. Bigger nodes represent larger gene sets. Thicker edges represent more overlapped genes.

FIGURE 8

Inositol phosphate metabolism pathway genes are highlighted in red (271158 is IPPK gene).

FIGURE 9

Phosphatidylinositol signaling system pathway genes are highlighted in red (271158 is IPPK gene).