Circular RNA 0004904 promotes autophagy and regulates the fused in sarcoma/vascular endothelial growth factor axis in preeclampsia.

Abstract

Circular (circ)RNA has been demonstrated to serve crucial roles in cell proliferation, differentiation and autophagy. However, to date, the function and mechanism of action of circRNA in preeclampsia have not been reported. The present study aimed to analyze the roles of circRNA‑0004904 in preeclampsia and to clarify its underlying pathogenic mechanism. The expression levels of circ‑0004904, microRNA (miR)‑570 and autophagy‑related12(ATG12) were detected by reverse transcription‑quantitative (RT‑q)PCR. In addition, the protein levels of ATG12, vascular endothelial growth factor(VEGF) and fused in sarcoma (FUS) were determined by western blot assay. The distribution of mRFP‑GFP‑LC3 in HTR8 and JEG3 cells was analyzed by confocal microscopy. Fluorescence insitu hybridization assay was utilized to identify the colocalization of circ‑0004904 and miR‑570. Cell proliferation was determined by 5‑ethynyl‑2'‑deoxyuridine assay, and invasion was evaluated by Matrigel invasion assay. The results of the present study demonstrated that the expression levels of circ‑0004904 were elevated in the placental tissues and plasma samples of patients with preeclampsia compared with those in the control group samples. Ectopic expression of circ‑0004904 promoted autophagy, but inhibited migration and proliferation of HTR8 cells compared with those in the negative control group. Silencing of circ‑0004904 inhibited autophagy, and induced migration and proliferation in JEG3 cells compared with those in the negative control group. In addition, circ‑0004904 regulated the levels of ATG12 via interaction with miR‑570. Furthermore, circ‑0004904 regulated the FUS/VEGF axis in HTR8 and JEG3 cells. In conclusion, circ‑0004904 was abnormally expressed in the plasma and placental tissues of patients with preeclampsia. In addition, circ‑0004904 was involved in the regulation of proliferation, invasion and autophagy in HTR8 and JEG3 cells. Thus, circ‑0004904 may be used as a potential diagnostic biomarker and therapeutic target for preeclampsia.