LNCRNA-ANG362 PROMOTES PULMONARY ARTERIAL HYPERTENSION BY REGULATING MIR-221 AND MIR-222

Background: Pulmonary arterial hypertension (PAH) is a life-threatening cardiopulmonary disorder. LncRNA-Ang362 (lnc-Ang362) regulates miR-221 and miR-222 in vascular smooth muscle cell proliferation, which can lead to PAH. The present study was designed to investigate the function and underlying mechanisms of lnc-Ang362 in PAH. Methods: The expression of lnc-Ang362, miR-221, and miR-222 in 15 PAH patients and 10 healthy controls was measured by qRT-PCR. Lnc-Ang362 overexpression vector and siRNA were transfected into human pulmonary arterial smooth muscle cells (HPASMCs), and cell proliferation, migration, and apoptosis rate were assessed. The protein expression of p-p65 and p-I kappa B alpha was measured by western blot. MiR-221 or miR-222 inhibitor was cotransfected with lnc-Ang362 overexpression vector into HPASMCs. Results: Data from the present study showed significantly increased lnc-Ang362, miR-221, and miR-222 expression in the lung tissues of patients with PAH and in hypoxic HPASMCs. Although overexpression of lnc-Ang362 promoted proliferation and migration of HPASMCs, inhibition of lnc-Ang362 had the opposite effect. In addition, apoptosis of HPASMCs significantly decreased after lnc-Ang362 overexpression and increased after lnc-Ang362 inhibition. Meanwhile, lnc-Ang362 upregulated miR-221 and miR-222 expression and activated the NF kappa B signaling pathway in HPASMCs. Moreover, miR-221 and the miR-222 inhibitor both attenuated the proliferation and migration effects of lnc-Ang362 and elevated apoptosis in these cells. Conclusion: Lnc-Ang362 played an important role in regulating the biological function of HPASMCs by promoting miR-221 and miR-222. Lnc-Ang362 thus may be a novel therapeutic lncRNA candidate for treating PAH.