Abstract
BackgroundGestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. CircRNA polyribonucleotide nucleotidyltransferase 1 (circ-PNPT1) has been found to be abnormally expressed in GDM patients. However, function and mechanism of circ-PNPT1 in GDM remain largely undefined.MethodsLevels of circ-PNPT1, microRNA (miR)-889-3p and PAK1 (p21 (RAC1) activated kinase 1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, migration and invasion were determined using cell counting kit-8 assay, flow cytometry, transwell and wound healing assays, respectively. The binding interaction between miR-889-3p and circ-PNPT1 or PAK1 was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy (TEM).ResultsCirc-PNPT1 was highly expressed in the placental tissues of GDM and high glucose (HG)-induced trophoblast cells. Knockdown of circ-PNPT1 reversed HG-induced arrest of trophoblast cell viability, migration, invasion and the promotion of cell apoptosis. Mechanistically, we confirmed circ-PNPT1 could promote the expression of PAK1, the target of miR-889-3p, by directly sponging miR-889-3p, and circ-PNPT1 regulated HG-induced trophoblast cell dysfunction by miR-889-3p/PAK1 axis. Further studies showed circ-PNPT1 was packaged into exosomes and could be internalized by surrounding trophoblast cells.ConclusionCirc-PNPT1 promoted HG-induced trophoblast cell biological dysfunction through miR-889-3p/PAK1 axis. Meanwhile, it could be transferred from HG-induced trophoblast cells to surrounding untreated cells via exosomes.
Highlights
Gestational diabetes mellitus (GDM), referring to glucose intolerance that is initiated during pregnancy, is the most common medical complication of pregnancy [1]
Trophoblast cells with normal biological function are critical for placenta development, targeting high glucose (HG)-induced trophoblast cell dysfunction may be an effective strategies for investigating the pathogenesis of GDM
Circ‐PNPT1 is highly expressed in placental tissues of GDM and HG‐stimulated trophoblast cells To elucidate the function of circ-PNPT1 in GDM, the expression profile of circ-PNPT1 was firstly detected
Summary
Gestational diabetes mellitus (GDM), referring to glucose intolerance that is initiated during pregnancy, is the most common medical complication of pregnancy [1]. GDM is highlighted by hyperglycemia and disorder of carbohydrate metabolism, aside from the immediate perinatal risk, GDM increases the risk of metabolic diseases in mothers and children [4, 5]. It is one of the main cause of maternal and neonatal adverse outcomes. Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. Function and mechanism of circ-PNPT1 in GDM remain largely undefined
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