A Systematic Bioinformatic Analysis of the miRNA Pathway in Inborn Errors of Amino Acid Metabolism Disorders

Area of Science:

• Biochemistry
• Genetics
• Bioinformatics

Background:

• Inborn errors of amino acid metabolism (IEAAM) cause toxic metabolite accumulation due to genetic defects.
• The role of microRNAs (miRNAs) in IEAAM pathogenesis is not well understood.
• A systematic bioinformatic analysis is needed to explore miRNA-gene interactions in IEAAM.

Purpose of the Study:

• To identify and validate specific miRNA-gene interactions involved in IEAAM.
• To elucidate the regulatory role of miRNAs in key metabolic pathways affected by IEAAM.
• To provide insights into potential miRNA-based therapeutic strategies for IEAAM.

Main Methods:

• Systematic literature search of PubMed and Scopus databases.
• Integration of identified miRNAs with metabolic genes using prediction tools (miRWalk, miRDB).
• Functional pathway analysis using KEGG, DisGeNET, and PubChem database integration for validation.

Main Results:

• A conserved network of six miRNAs (mmu-miR-409-5p, hsa-miR-3944-3p, rno-miR-125b-5p, hsa-miR-145-5p, hsa-miR-5195-3p, hsa-miR-1202) was identified.
• These miRNAs were bioinformatically validated to target key metabolic genes (FAH, DBT, CBS, PSAT1, ARG1).
• Enrichment in metabolic pathways and association with clinical phenotypes like epilepsy and metabolic crises were observed.

Conclusions:

• This study presents the first systematic evidence of a conserved miRNA-gene regulatory network in aminoacidopathies.
• The identified miRNAs offer novel insights into the epigenetic modulation of metabolic pathways in IEAAM.
• These findings highlight potential targets for future miRNA-based therapeutic interventions in IEAAM.