Circ_0005372 targets the miR-153-3p/ITGB3 axis to stimulate the PI3K/AKT signaling pathway to facilitate the occurrence and development of congenital heart disease and pulmonary arterial hypertension in children.

Abstract

Background: Congenital heart disease (CHD) is the most common and highest incidence of congenital malformations in newborn infants. Pulmonary arterial hypertension (PAH) is the most serious complication associated with CHD. It is a great threat to the safety and health of newborns.

Methods: The expression of circ_0005372, miR-153-3p, and ITGB3 were detected by Real-time quantitative PCR (RT-qPCR) and western blot (WB). MTT and EdU assays were used to evaluate the viability and proliferation of human pulmonary artery smooth muscle cells (HPASMC). Migration and invasion abilities were determined by wound healing and Transwell assays. Pull down and RNA Immunoprecipitation (RIP), and dual luciferase reporter gene assays were used to detect targeting relationships of circ_0005372, miR-153-3p, and ITGB3.

Results: Plasma samples from 27 healthy, CHD, and PAHCHD pairs of newborns were collected. Circ_0005372 was highly expressed in PAHCHD patient samples and HPASMCs under hypoxic conditions. Knockdown of circ_0005372 inhibited HPASMCs viability, proliferation, migration, and invasion. Circ_0005372 targeted miR-153-3p and showed a negative correlation. The inhibitory effect of silencing circ_0005372 on the HPASMCs was reversed by miR-153-3p inhibitor. MiR-153-3p negatively regulated ITGB3, and overexpression of ITGB3 abolished the effect of miR-153-3p in hypoxia-treated HPASMCs. Circ_0005372 could regulate the PI3K/AKT signaling pathway through miR-153-3p/ ITGB3.

Conclusion: In summary, circ_0005372 mediates the expression of ITG3B via targeting miR-153-3p, thereby stimulating the PI3K/AKT signaling pathway, helping the proliferation, migration, and invasion of HPASMCs and accelerating the deterioration of PAHCHD.