Downregulated hsa_circ_005243 induced trophoblast cell dysfunction and inflammation via β-catenin and NF-κB pathways in gestational diabetes mellitus

Abstract

Background: Gestational diabetes mellitus(GDM) is a common obstetric pregnancy complication, which poses a serious threat to the health of pregnant women and newborns. The specific etiology and pathogenesis of this disease have not been fully clarified, it is reported to be related with insulin resistance, inflammatory response and genetic factors etc. Circular RNA(circRNA) is a special kind of non-coding RNA, which have been attracted much attention in recent years. It has been reported that circRNAs may play a regulatory role in pregnancy-related diseases, including GDM. Methods: Previously we reported a circRNA, hsa_circ_005243, which was identified by RNA-sequencing. In this study we detected its expression in 20 GDM pregnant women and 20 normal controls using quantitative reverse transcription polymerase chain reaction analysis. Further in vitro experiments were conducted after hsa_circ_005243 knockdown in HTR8-S/Vneo cells, cell proliferation and migration ability was tested, the secretion of inflammatory factors (TNF-α and IL-6) were detected by ELISA. Then we detected the expression of β-catenin and increased nuclear factor kappa-B (NF-κB) signaling pathways which was related to GDM in the mechanism study. Results: We found the expression of hsa_circ_005243 was significantly reduced both in the placenta and plasma of GDM pregnant women. Knockdown of hsa_circ_005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) were observed after hsa_circ_005243 depletion. Further mechanism experiments showed that knockdown of hsa_circ_005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation. Conclusions: Collectively, our study showed that down-regulation of hsa_circ_005243 might be associated with the pathogenesis of GDM through regulating β-catenin and NF-κB signal pathways and suggest a new potential therapeutic target for GDM.