Mir-181b-5p Inhibits Trophoblast Cell Migration And Invasion Through Targeting S1pr1 In Multiple Abnormal Trophoblast Invasion-Related Events

Normal placentation and successful maintenance of pregnancy depend on the successful migration and invasion of trophoblasts into maternal tissues. Previous studies reported that microRNAs (miRs) are expressed in trophoblasts, and can regulate their migration and invasion. The present study aimed to investigate miR-181b-5p function in HTR-8/SVneo trophoblasts and explore its underlying mechanism in the pathogenesis of multiple abnormal trophoblast invasion-related events. Reverse-transcription quantitative PCR and western blotting were used to test the expression of miR-181b-5p and sphingosine-1-phosphate receptor 1 (S1PR1) in samples of multiple abnormal trophoblast invasion-related events. Transwell invasion and wound healing assays were performed to determine cell invasion and migration abilities. A luciferase reporter assay was conducted to identify the downstream target of miR-181b-5p. Overexpression of miR-181b-5p suppressed HTR-8/SVneo cell migration and invasion, whereas inhibition of miR-181b-5p induced an opposite effect. The S1PR1 gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3 '-untranslated region of S1PR1 and suppressed its expression. Moreover, overexpression of S1PR1 reversed the inhibitory effect of miR-181b-5p. Taken together, ectopic expression of miR-181b-5p impaired the migration and invasion of trophoblasts by directly targeting S1PR1, thereby providing new insights into the pathogenesis of multiple abnormal trophoblast invasion-related events.