Hsa_circ_0015382 is involved in the pathogenesis of preeclampsia by mediating THBS2 expression

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy that causes significant maternal and perinatal morbidity and mortality. Circular RNA (circRNA) hsa_circ_0015382 is associated with the pathogenesis of PE, but its underlying regulatory mechanism remains to be explored.

Methods: Relative RNA levels of hsa_circ_0015382, microRNA-616-3p and thrombospondin-2 (THBS2) were detected by quantitative reverse transcription-polymerase chain reaction. In vitro regulatory effects of hsa_circ_0015382 on the proliferation, migration, invasion and angiogenesis of trophoblasts were evaluated by CCK-8, flow cytometry for cell cycle, EdU, transwell, wound healing and HUVEC tube formation assays, respectively. Targeting interaction was verified by dual-luciferase reporter and RNA immunoprecipitation assays.

Results: Hsa_circ_0015382 was highly expressed in placental tissues from PE patients. Upregulation of hsa_circ_0015382 repressed trophoblast proliferation, migration, invasion and lowered trophoblast-induced HUVEC tube formation. Hsa_circ_0015382 was validated as a miR-616-3p Sponge and miR-616-3p targeted THBS2. Hsa_circ_0015382 could mediate trophoblast proliferation, migration, invasion and regulate trophoblast-induced HUVEC tube formation by sponging miR-616-3p and regulating THBS2 expression.

Conclusion: Hsa_circ_0015382 is associated with the pathogenesis of PPE by regulating the miR-616-3p/THBS2 axis.

Highlights: Hsa_circ_0015382 is overexpressed in preeclampsia patients. Hsa_circ_0015382 inhibits trophoblast proliferation, migration, invasion and decreases trophoblast-induced HUVEC tube formation. Hsa_circ_0015382 interacts with miR-616-3p to regulate THBS2 expression.