Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 54 12 2025 12 31 2754 2763 Akram Gholipour Cardiogenetic Research Center, Rajaie Cardiovascular Institute, Tehran, Iran Molood Farsi Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran Faezeh Sari Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran Zahra Khajali 1. Cardiogenetic Research Center, Rajaie Cardiovascular Institute, Tehran, Iran 2. Congenital Heart Diseases Research Center, Rajaie Cardiovascular Institute, Tehran, Iran Majid Maleki Cardiogenetic Research Center, Rajaie Cardiovascular Institute, Tehran, Iran Mahshid Malakootian 1. Cardiogenetic Research Center, Rajaie Cardiovascular Institute, Tehran, Iran 2. Vascular Disease and Thrombosis Research Center, Rajaie Cardiovascular Institute, Tehran, Iran 2025 05 02 2025 10 19 Background: Pulmonary arterial hypertension (PAH) is characterized by high blood pressure in the lungs due to obstruction of small pulmonary arteries. Its exact cause is unknown. We aimed to identify specific genes, signaling pathways, and microRNAs (miRNAs) as novel diagnostic biomarkers for PAH progression. Methods: We analyzed differentially expressed genes (DEGs) from PAH and control samples in the GSE144932 and GSE131793 datasets using GEO2R. We performed GO enrichment and KEGG pathway analyses. miRNAs targeting common DEGs were identified using miRDB and TargetScan. Results: MYLK and CLU were upregulated in both datasets, implicating calcium signaling and coagulation pathways, respectively. In silico analysis showed that miR-9-5p, miR-3179, and miR-580-3p potentially target MYLK; miR-369-3p potentially targets CLU; and miR-499a-5p potentially targets both. Conclusion: This study identifies MYLK and CLU, and their associated miRNAs (miR-9-5p, miR-3179, miR-580-3p, miR-499a-5p, and miR-369-3p), as potential noninvasive diagnostic biomarkers for PAH, requiring experimental validation.  https://ijph.tums.ac.ir/index.php/ijph/article/view/38971 https://ijph.tums.ac.ir/index.php/ijph/article/download/38971/8735