Study on the Regulation of Trophoblast Activity by Abnormally Expressed lncRNA CCDC144NL-AS1 in Patients with Gestational Diabetes Mellitus.

Abstract

Gestational diabetes mellitus (GDM) is a common complication in pregnant women. The growth and differentiation of trophoblast cells determine the function of the placenta, and therefore further affect the transport of nutrients to the fetus. lncRNA Coiled-Coil Domain Containing 144 N-Terminal-Like antisense1 (CCDC144NL-AS1) was reported to be abnormally expressed in GDM, but its function and mechanism remain undefined. This study aimed to reveal the expression of CCDC144NL-AS1 in GDM and evaluate its significance in disease development. The expression of CCDC144NL-AS1 in serum and placenta tissues of GDM patients and healthy pregnant women was evaluated using PCR. The effect of CCDC144NL-AS1 on the proliferation, migration, and invasion of trophoblast cells was evaluated with CCK8 and Transwell assay. The mechanism of the interaction between CCDC144NL-AS1 and miR-143-3p was assessed by luciferase reporter assay and cell transfection. CCDC144NL-AS1 was upregulated in GDM patients, which discriminated GDM patients from healthy pregnant women with high sensitivity and specificity and was positively correlated with the insulin resistance indexes. In trophoblast cells, high glucose exposure induced increased CCDC144NL-AS1 and suppressed cell proliferation, migration, and invasion. Silencing CCDC144NL-AS1 could alleviate the inhibitory effect of high glucose, while the knockdown of miR-143-3p reversed the effect of CCDC144NL-AS1. In conclusion, upregulated CCDC144NL-AS1 served as a diagnostic biomarker of GDM and regulated the development of trophoblast cells via negatively modulating miR-143-3p.