MiRNA Expression Profile as a Potential Biomarker for Idiopathic Congenital Talipes Equinovarus: An Exploratory Study

The etiology of Idiopathic Congenital Talipes Equinovarus (ICTEV) remains poorly understood. Several theories have been proposed, including genetic factors. Unlike genes, which are essentially static in composition and size, transcriptome or microRNA (miRNA) varies greatly and might be influenced by multiple variables. This research aims to determine the expression of MiRNA that influences the occurrence of ICTEV in the Indonesian population.

A cross-sectional study was conducted using samples obtained from patients with ICTEV under the age of three years. Transcriptome profile evaluation was carried out through Nanostring analysis using nSolver Analysis to obtain miRNAs that play a role in the regulation of ICTEV.

Among the 25 most upregulated miRNAs identified, two candidates were selected: miR-584-5p and miR-125a-3p. There were just two miRNAs which were downregulated namely miR-26a-5p and miR-548d-5p. Bioinformatics analysis using Diana-miRPathv4 for upregulated microRNA using gene union and pathway union, revealed results related to the regulation of actin cytoskeleton, HIF-1 signaling pathway, Hippo signaling pathway and TGF-β signaling pathway. Bioinformatics analysis for downregulated miRNAs found that these miRNAs are affecting TGF-β regulation, actin cytoskeleton regulation and apoptotic pathway. These miRNAs act in the TGF-β signaling pathway which regulate cellular processes such as proliferation, apoptosis, differentiation, and extracellular matrix formation. These findings suggest a potential role of TGF-β signaling in the pathogenesis of ICTEV. Meanwhile, the other intersection pathway, the actin cytoskeleton is related to Filamin B (FLNB), in which mutation on FLNB causes skeletal deformity, dysregulation of muscle differentiation and presenting ICTEV appearance.

miR-584-5p, miR-125a-3p, miR-26a-5p and miR-548d-5p were identified as potential biomarker candidates for detecting ICTEV. In the development of biomarkers, validation of these discovered miRNA candidates is required, including expression testing and further analysis of their individual involvement in regulating the ICTEV-related genes.