miR-PAIR: microRNA-protein analysis of integrative relationship for the identification of significantly working miRNAs

• Published in: Biochimica et biophysica acta. General subjects 2025-02, Vol.1869 (2), p.130746, Article 130746
• Main Authors: Akai, Mizuki, Maeda, Yuki, Kawami, Masashi, Yumoto, Ryoko, Takano, Mikihisa, Uchida, Yasuo
• Format: Article
• Language: English
• Subjects: A549 Cells; Bioinformatics; Bleomycin - pharmacology; Gene Expression Profiling; Humans; Methotrexate - pharmacology; microRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Proteomics; Proteomics - methods; RNA-sequence
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130746

MicroRNAs (miRNAs), which are small non-coding RNAs, are recognized as important significant endogenous bio-molecules that regulate the post-transcriptional processes of target genes. However, predictive methods for significantly working miRNAs are poorly understood. The present study aimed to establish a novel method, miRNA protein analysis of integrative relationship (miR-PAIR), for the identification of effectively working miRNAs involved in physiological or pathological events. To establish the miR-PAIR, comprehensive expression data of miRNAs and proteins were obtained using small RNA-sequence and quantitative proteomics approach in the alveolar epithelial cell line, A549 treated with bleomycin (BLM) and methotrexate (MTX) as pulmonary toxic drugs. Differentially expressed miRNAs and proteins were integrated using TargetScan, a freely available web tool for predicting the target gene of miRNAs. Next, the enrichment of the integrated miRNA-protein pairs was analyzed, followed by the determination of significantly working miRNAs in BLM- and MTX-induced protein expression changes. The miR-PAIR method identified 22 downregulated and 9 upregulated miRNAs. Among them, miR-493-5p (p = 1.71E-05), an upregulated miRNA, suppressed approximately 70 % of the target proteins, and miR-598-3p (p = 1.1E-03), a downregulated miRNA, canceled 50 % of the target protein expression changes induced by BLM and MTX. Thus, a miR-PAIR could be an effective method to identify significantly working miRNAs associated with biological events such as drug-induced lung injury. [Display omitted] •A novel microRNA prediction system was established as miR-PAIR.•A miR-PAIR can determine the priority of significant microRNAs.•microRNAs estimated by a miR-PAIR were validated.•Output of miR-PAIR was different from that of miRNA-mRNA paring analysis.