Circ_0085296 suppresses trophoblast cell proliferation, invasion, and migration via modulating miR-144/E-cadherin axis

Background: Circular RNAs (circRNAs) have been revealed to be important regulators in the biological behavior of cells, and aberrant circRNAs may be associated with the etiology of pre-eclampsia (PE). However, the role and underlying molecular mechanisms of circ_0085296 in PE remain unclear.

Methods: The expression of circ_0085296, microRNA (miR)-144, and E-cadherin was detected using quantitative real-time polymerase chain reaction and western blot, respectively. Cell proliferation, migration, and invasion were analyzed by cell counting kit-8, colony formation and transwell assay. The interaction between miR-144 and circ_0085296 or E-cadherin was analyzed by the dual-luciferase reporter assay and pull-down assay.

Results: Circ_0085296 was elevated in PE placental tissues, knockdown of circ_0085296 promoted trophoblast cell proliferation, invasion, and migration, while circ_0085296 up-regulation showed opposite effects. MiR-144 was down-regulated in PE placental tissues, and restoration of miR-144 induced proliferation, invasion, and migration in trophoblast cells. Further mechanistic analysis found miR-144 directly bound to circ_0085296 and E-cadherin, and circ_0085296 functioned as a sponge of miR-144 to regulate E-cadherin expression. Furthermore, miR-144 inhibition or E-cadherin overexpression attenuated the effectsof circ_0085296 on cell processes in trophoblast cells.

Conclusion: Circ_0085296 inhibited trophoblast cell proliferation, invasion, and migration via regulating miR-144/E-cadherin axis, providing a novel insight into the pathogenesis of PE and a new prospective therapeutic target for PE patients.