Hsa_circ_0006260 Mediates Trophoblast Function by Fibronectin Type III Domains Containing Protein 5 via Interacting...

A series of studies have confirmed the relationship between circular RNAs (circRNAs) and metabolic diseases. Hsa_circ_0006260 has been reported to be lowly expressed in the placenta of gestational diabetes mellitus (GDM) patients, but the underlying mechanism and its biological functions remain obscure. Placental tissues were collected from 37 pregnant women with normal glucose tolerance (NGT) and 37 pregnant women with GDM. Expression changes of hsa_circ_0006260 in placentas and high glucose (HG)-stimulated HTR-8/SVneo cells were detected using real-time quantitative polymerase chain reaction. Cell viability and migration were determined by cell counting and transwell assays, respectively. Measurement of cytokines was done by enzyme-linked immunosorbent assay. Cell apoptosis was estimated by flow cytometry assay. The molecular mechanisms were identified using dual-luciferase reporter and RNA-binding protein immunoprecipitation assays. Hsa_circ_0006260 expression was remarkably lowered in GDM patient-derived placentas and HG-stimulated HTR-8/SVneo cells. Functionally, hsa_circ_0006260 overexpression weakened HG-mediated repression of HTR-8/SVneo cell viability and migration, as well as promotion of HTR-8/SVneo cell inflammatory response and apoptosis. Mechanistically, hsa_circ_0006260 functioned as a miR-770-5p decoy to mediate fibronectin type III domains containing protein 5 (FNDC5) expression. Ectopic expression of miR-770-5p weakened hsa_circ_0006260 overexpression-mediated repression of HG-induced HTR-8/SVneo cell dysfunction. Also, FNDC5 knockdown lessened miR-770-5p overexpression-mediated promotion of HG-induced HTR-8/SVneo cell dysfunction. Our findings manifested a novel mechanism by which hsa_circ_0006260 could lower HG-induced HTR-8/SVneo cell dysfunction by upregulating FNDC5 via binding to miR-770-5p, which shed new light on circRNA mediated GDM pathogenesis.