Work

Exploratory mRNA and microRNA profiling identifies transcriptomic alterations in the PIK3CA-related overgrowth spectrum

Year: 2026

Type: article

Abstract: Background: gene, characterized by tissue overgrowth affecting multiple organs, including the skin, adipose tissue, blood vessels, bones, and nervous system. Although constitutive hyperactivation of PI3K-AKT-mTOR signaling in PROS promotes abnormal tissue development, remodeling, and segmental overgrowth, the downstream signaling networks are highly complex, and the precise molecular mechanisms underlying tissue overgrowth remain incompletely understood. Methods: In this exploratory study, we investigated molecular alterations associated with overgrowth in PROS by profiling mRNA and microRNA expression in fibroblasts derived from affected skin (pv-Fibro) and unaffected skin (non-pv-Fibro) from the same patient. Additionally, fibroblasts from three healthy individuals were pooled and analyzed as a single control sample. Results: We identified 24,034 human mRNAs using microarray-based gene expression profiling. Ten mRNAs were selected as candidate lesion-associated upregulated genes in pv-Fibro (≥5-fold vs. nc-Fibro and <2-fold change in non-pv-Fibro vs. nc-Fibro). In contrast, three mRNAs were selected as candidate lesion-associated downregulated genes in pv-Fibro (≤0.2-fold vs. nc-Fibro and >0.5-fold in non-pv-Fibro vs. nc-Fibro). For miRNA profiling, 4,603 human microRNAs were analyzed. hsa-miR-146a-5p was markedly upregulated in pv-Fibro (≥5-fold vs. nc-Fibro and <2-fold change in non-pv-Fibro vs. nc-Fibro), while hsa-miR-146b-5p was markedly downregulated (≤0.2-fold vs. nc-Fibro and >0.5-fold in non-pv-Fibro vs. nc-Fibro). Discussion: The observed changes in mRNA and miRNA expression represent candidate molecular alterations associated with inflammatory and tissue remodeling pathways in PROS pathology.

Source: Frontiers in Genetics

DOI: 10.3389/fgene.2026.1935186