Dysregulation of miR-330-3p is Involved in the Occurrence and Development of Pulmonary Arterial Hypertension Caused by Congenital Heart Disease

Anatol J Cardiol. 2025 Apr 21;29(6):291-299. doi: 10.14744/AnatolJCardiol.2025.4807. Online ahead of print.

Abstract

Background: The study aimed to investigate the expression of miR-330-3p and its clinical and functional performance in congenital heart disease-associated pulmonary hypertension (CHD-PAH).

Methods: The expression of miR-330-3p in CHD-PAH and hypoxiatreated human pulmonary artery smooth muscle cells (HPASMCs) was assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The receiver operating curve was conducted to evaluate the clinical diagnostic value of serum miR-330-3p in CHD-PAH. In cytology, CCK-8 and Transwell migration assays were performed to assess the func-tional role of miR-330-3p in hypoxia-induced HPASMCs. The online TargetScan database and dualluciferase reporter assays were employed to explore the downstream target of miR-330-3p.

Results: Compared with healthy controls and patients without PAH, miR-330-3p expres-sion was upregulated in patients with PAH. Serum miR-330-3p expression has relatively high area under the curve (AUC) values in differentiating CHD-PAH patients from con-genital heart disease (CHD) patients and healthy individuals. Silencing miR-330-3p weakened the increased cell proliferation, migration, and inflammation caused by hypoxia in HPASMCs. KLF-10 was identified as a putative target of miR-330-3p. Knockdown of KLF-10 could partially reverse the influence of miR-330-3p knockdown in hypoxiainduced HPASMCs.

Conclusion: Upregulation of miR-330-3p might have diagnostic value for predicting individuals suffering from CHD-PAH. Silencing of miR-330-3p reduced the excessive proliferation, migration, and inflammation of hypoxiaexposed HPASMCs by targeting KLF10, which is expected to be a novel small-molecule drug for the targeted treatment of CHD-PAH.