Long noncoding RNA SNHG6 contributes to ventricular septal defect formation via negative regulation of miR-101 and activation of Wnt/β-catenin pathway.

Abstract

This study aimed to investigate the role and regulatory mechanism of small nucleolar RNA host gene 6 (SNHG6), a long noncoding RNA, in the formation of ventricular septal defect (VSD). The expression of SNHG6 in fetal cardiac tissues with VSD, mouse heart embryo development and the differentiation of P19 cells into cardiomyocytes were determined. Moreover, the effect of aberrant expression of SNHG6 on P19 cell proliferation, cell cycle, apoptosis and differentiation was further analyzed to explore the role of SNHG6 in affecting myocardial development. Furthermore, the regulatory mechanism between SNHG6 and miR-101 as well as between SNHG6 and activation of Wnt/β-catenin pathway was investigated. SNHG6 was upregulated in fetal cardiac tissues with VSD, and decreased in the embryonic development of mice and differentiation of P19 cells into cardiomyocytes. Overexpression of SNHG6 inhibited P19 cell proliferation and induced apoptosis, as well as promoted cell differentiation into cardiomyocytes. Furthermore, SNHG6 could negative regulate the expression of miR-101, and the effects of SNHG6 on the modulation of P19 cell function were through negative regulation of miR-101. In addition, overexpression of SNHG6 activated Wnt/β-catenin pathway, which was reversed after overexpression of SNHG6 and miR-101 synchronously. Our study reveals that SNHG6 may contribute to VSD formation via negative regulation of miR-101 and activation of Wnt/β-catenin pathway. SNHG6 may constitute a potential therapeutic target in this disease.