Decrease in LINC00963 attenuates the progression of pulmonary arterial hypertension via microRNA-328-3p/profilin 1...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pulmonary Medicine

Background:

• Pulmonary arterial hypertension (PAH) is a severe disease marked by vascular hyperplasia and remodeling.
• Long noncoding RNA LINC00963 is known to influence cell proliferation in cancer, but its role in PAH is understudied.

Purpose of the Study:

• To investigate the function of LINC00963 in the progression of pulmonary arterial hypertension.
• To explore the regulatory mechanism involving LINC00963, microRNA-328-3p, and profilin 1 in PAH.

Main Methods:

• Quantitative real-time PCR and western blotting to assess gene and protein expression.
• Cell viability and migration assays on hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs).
• Dual-luciferase reporter assay and a mouse model of PAH to confirm molecular interactions and in vivo effects.

Main Results:

• LINC00963 and profilin 1 (PFN1) were highly expressed, while microRNA (miRNA)-328-3p was lowly expressed in hypoxia-induced PASMCs and a PAH mouse model.
• Silencing LINC00963 or using miR-328-3p mimics repressed PASMC viability, migration, and expression of VEGF, FGF-2, and HIF-α.
• The effects of LINC00963 silencing were partially reversed by inhibiting miR-328-3p or overexpressing PFN1, indicating a regulatory pathway.

Conclusions:

• LINC00963 promotes PAH progression.
• The LINC00963/miR-328-3p/PFN1 axis plays a critical role in the pathogenesis of PAH.
• Silencing LINC00963 ameliorates PAH by modulating the miR-328-3p/PFN1 pathway.