Braz J Cardiovasc Surg. 2026 Sep 21;41(3):20250181. doi: 10.21470/1678-9741-2025-0181.
ABSTRACT
INTRODUCTION: This study explored the function and molecular mechanism of long non-coding ribonucleic acid taurine up-regulated gene 1 (TUG1) in children with ventricular septal defect (VSD).
METHODS: To establish an in vivo VSD model, 10 pregnant mice were administered valproic acid via intraperitoneal injection (VSD group, n = 10). Another 10 pregnant mice were used as the control group and administered 0.9% sodium chloride solution via intraperitoneal injection. Subsequently, the cardiac function and cardiac tissue histopathological characteristics in both groups were evaluated. TUG1, miR-222-3p, and hypoxia-inducible factor 1-alpha subunit inhibitor (HIF1AN) expression levels in cardiac tissues were tested. P19 cells were chosen to simulate VSD in vitro model, and the cell progression was tested. P19 cells were induced to differentiate into cardiomyocytes with dimethyl sulfoxide, and test of the shape and beating frequency of cardiomyocytes was conducted. Left ventricular fractional shortening, ejection fraction, and systolic and diastolic thickness of the cardiac anterior wall were significantly reduced in VSD fetal mice. VSD formation, aortic overlay, and dysplasia were observed.
RESULTS: TUG1 and HIF1AN were upregulated, and miR-222-3p was downregulated in VSD mice. Silencing TUG1 or HIF1AN or elevating miR-222-3p facilitated P19 cell progression and differentiation, whereas lowering miR-222-3p did the opposite. TUG1 was a molecular sponge of miR-222-3p, which targeted HIF1AN. Elevating HIF1AN reversed the impacts of silencing TUG1 or elevating miR-222-3p on P19 cells.
CONCLUSIONS: The findings of this study could offer a new insight into the molecular basis of VSD and lay the groundwork for new diagnostic techniques.
PMID:42776135 | DOI:10.21470/1678-9741-2025-0181