CircPAPPA Regulates the Proliferation, Migration, Invasion, Apoptosis, and Cell Cycle of Trophoblast Cells Through the miR-3127-5p/HOXA7 Axis.

Abstract

Abnormal function of trophoblast cells is one of the important causes of preeclampsia (PE). Circular RNA (circRNA) is thought to be involved in the regulation of various diseases progression, including PE. However, the role of circRNA pregnancy-associated plasma protein A (circPAPPA) in PE is less studied. The expression levels of circPAPPA, miR-3127-5p, and homeobox A7 (HOXA7) were determined by quantitative real-time PCR. Cell proliferation was evaluated using MTT assay and colony formation assay. Besides, flow cytometry was used to detect cell apoptosis and cell cycle distribution. In addition, the interaction between miR-3127-5p and circPAPPA or HOXA7 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircPAPPA was lowly expressed in the placental tissues of PE patients. Knockdown of circPAPPA inhibited proliferation, migration, and invasion, while induced apoptosis and cell cycle arrest in trophoblast cells. MiR-3127-5p could be targeted by circPAPPA, and its inhibitor reversed the effect of circPAPPA silencing on the biological function of trophoblast cells. Moreover, HOXA7 was a target of miR-3127-5p. HOXA7 overexpression reversed the effect of miR-3127-5p on the biological function of trophoblast cells. Our research indicated that circPAPPA positively regulated the biological function of trophoblast cells to mediate the progression of PE by miR-3127-5p/HOXA7 axis, which suggested that circPAPPA might be a potential biomarker for PE.