Our results demonstrated that CASC2 was down-regulated in response to hypoxia in PASMCs, and CASC2 could inhibit hypoxia-induced proliferation and migration of PASMCs by regulating the miR-222/ING5 axis to suppress vascular remodeling, indicating a novel insight and therapeutic strategy for hypoxia-induced PAH. This evidence concerns the gene CASC2 and pulmonary arterial hypertension.