, Jin Li 2
, Yiran Luo 3
, Tianzong Li 4
, Ya Wang 5
, Xiaolan He 5
, Xia Tan 3
, Manxia Liu 3
, Xinghui Liu 6
, Jianmei Shen 7
2Department of Cardiovascular Medicine, The People’s Hospital of Baoying City, Yangzhou, China
3Department of Cardiac Function, Guizhou Provincial People’s Hospital, Guiyang, China
4Department of Cardiovascular Interventional Radiology, Guizhou Provincial People’s Hospital, Guiyang, China
5Department of Pathology, Guizhou Provincial People’s Hospital, Guiyang, China
6Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, China
7Emergency Internal Medicine, Nantong Haimen People’s Hospital, Nantong, China
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.