Overexpression of microRNA-186 inhibits angiogenesis in retinoblastoma via the Hedgehog signaling pathway by targeting ATAD2.

Retinoblastoma (RB) represents an aggressive malignancy in the eye during the period of infancy and childhood. We delineated the ability of microRNA-186 (miR-186) to influence viability, invasion, migration, angiogenesis, and apoptosis of RB via the Hedgehog signaling pathway by targeting AAA domain-containing protein 2 (ATAD2). The microarray-based analysis was adopted to identify differentially expressed genes (DEGs) related to RB. Subsequently, RB cells were treated with miR-186 mimic, miR-186 inhibitor, or si-ATAD2. The expression of miR-186, ATAD2, Hedgehog signaling pathway-related genes were evaluated, and the target relationship between miR-186 and ATAD2 was verified. Finally, cell proliferation, invasion, migration, apoptosis, and angiogenesis were assessed. ATAD2 was identified as a DEG and modulated by miR-186. Moreover, we revealed that ATAD2 was highly expressed, whereas miR-186 was lowly expressed, and the Hedgehog signaling pathway was activated in RB. Then, ATAD2 as a putative target of miR-186 was validated using a luciferase assay. miR-186 mimic or siRNA-ATAD2 in RB cells reduced cell viability, invasion, and migration coordinating with elevated apoptosis via impairing the Hedgehog signaling pathway, where repressed angiogenesis was observed. Overexpression of miR-186 attenuates RB via the inactivation of the Hedgehog signaling pathway by downregulating ATAD2.