LncRNA small nucleolar RNA host gene 5 inhibits trophoblast autophagy in preeclampsia by targeting microRNA-31-5p and promoting the transcription of secreted protein acidic and rich in cysteine

Abstract

ABSTRACT Preeclampsia (PE) is a pregnancy-related complication. Dysregulation of long non-coding RNAs (lncRNAs) contributes to the pathogenesis of PE. The current study sought to investigate the effect of lncRNA small nucleolar RNA host gene 5 (SNHG5) on trophoblast autophagy in PE. A PE mouse model was established, followed by detection of parameters such as blood pressure, proteinuria, triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein, observation of alterations of mouse placenta and kidney, and detection of B-cell chronic lymphocytic leukemia/lymphoma-2, Bcl-2-associated X protein, and SNHG5 expression patterns. The expressions of LC3, Beclin-1, and p62 in the placenta of PE mice were detected. Moreover, the SNHG5 expression was downregulated in the established HTR-8/SVneo trophoblast model, followed by evaluation of cell proliferation, apoptosis, and autophagy. After combination treatment with 3-MA (an autophagy inhibitor) and si-SNHG5, the behaviors of HTR-8/SVneo cells were observed. The binding relations between SNHG5 and miR-31-5p, and miR-31-5p and SPARC were verified. The expressions of miR-31-5p and SPARC in the placenta of mice and trophoblasts were determined. Our results demonstrated a poor expression of lncRNA SNHG5 in PE mice. SNHG5 overexpression reduced the PE phenotype and tissue damage in mice. SNHG5 silencing reduced the proliferation, migration, and invasion of trophoblasts, but elevated apoptosis and autophagy. SNHG5 sponged miR-31-5p to promote SPARC transcription. Additionally, miR-31-5p knockdown or 3-MA treatment reverted the stimulative effect of SNHG5 silencing on trophoblast autophagy. Collectively, our study demonstrated that lncRNA SNHG5 alleviated the PE phenotype and inhibited trophoblast autophagy by sponging miR-31-5p and promoting SPARC transcription.