Role of hsa-miR-122-5p in chronic thromboembolic pulmonary hypertension and chronic thromboembolic disease: Targeting PIK3CG in the PI3K/Akt signaling pathway

Chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease (CTED) are related conditions with distinct clinical outcomes. However, reliable molecular biomarkers for their diagnosis and differentiation remain limited. This study aimed to explore differentially expressed microRNAs (miRNAs) in peripheral blood to identify potential diagnostic and therapeutic biomarkers. Peripheral blood samples were collected from patients with CTEPH, CTED, and healthy controls. RNA sequencing was performed to identify differentially expressed miRNAs. Diagnostic performance was evaluated using receiver operating characteristic analysis. Functional enrichment analyses were conducted to explore the biological pathways associated with key miRNAs. A competing endogenous RNA network was constructed to investigate potential miRNA-target interactions. Compared with CTED, 34 miRNAs were upregulated and 33 downregulated in CTEPH. In CTEPH versus healthy controls, 35 miRNAs were upregulated and 11 downregulated. Among them, hsa-miR-122-5p, hsa-miR-182-5p, and hsa-miR-183-5p exhibited notable diagnostic accuracy, with area under the curve values of 0.733, 0.933, and 0.867, respectively. Functional enrichment analysis implicated these miRNAs in key signaling pathways, including phosphoinositide 3-kinase/Akt and adenosine monophosphate-activated protein kinase. The competing endogenous RNA network suggested that hsa-miR-122-5p may target PIK3CG, implicating it in the pathogenesis of CTEPH. This study identifies hsa-miR-122-5p, hsa-miR-182-5p, and hsa-miR-183-5p as promising biomarkers for the diagnosis and potential treatment of CTEPH. These findings provide new insights into the molecular mechanisms underlying CTEPH and CTED and may contribute to improved clinical management of these conditions.