Circ_0011460 upregulates HTRA1 expression by sponging miR‐762 to suppress HTR8/SVneo cell growth, migration, and invasion

Abstract

Aberrant expression of circular RNAs (circRNAs) during placental development could affect fetal growth and contribute to preeclampsia (PE). Circ_0011460 was found to be differentially expressed in placental samples of PE. However, the exact function and mechanism of circ_0011460 in PE process remain largely undefined. Levels of circ_0011460, microRNA (miR)-762, and high-temperature requirement-A serine peptidase 1 (HTRA1) were detected using quantitative real-time polymerase chain reaction and Western blot. In vitro experiments in HTR8/SVneo cells were conducted using cell counting kit-8, wound healing, transwell, flow cytometry and Western blot assays. The direct interactions between miR-762 and circ_0011460 or HTRA1 were verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Circ_0011460 possessed a loop structure and was highly expressed in placental tissues of PE patients. Overexpression of circ_0011460 greatly suppressed HTR8/SVneo cell proliferation, migration, and invasion, and accelerated cell apoptosis. While circ_0011460 knockdown yielded the opposite trends on above biological behaviors. Mechanistically, we confirmed that circ_0011460 could up-regulate HTRA1 expression via serving as a sponge of miR-762. Further rescue studies demonstrated that circ_0011460 exerted its roles via targeting miR-762, and miR-762 promoted HTR8/SVneo cell growth, migration and invasion via regulating HTRA1. In all, circ_0011460 suppressed HTR8/SVneo cell growth, migration, and invasion via miR-762/HTRA1 axis, suggesting a new insight into the pathogenesis of PE.