hsa_circWDR37_016 Regulates Hypoxia-Induced Proliferation of Pulmonary Arterial Smooth Muscle Cells

Pulmonary arterial hypertension (PAH) is characterized by abnormal remodeling of pulmonary vessel walls caused by excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Our previous clinical studies have demonstrated the importance of the downregulated circRNA in PAH. However, the role of upregulated circRNAs is still elusive. Here, we identified the upregulated circRNA in PAH patients, hsa_circWDR37_016 (circWDR37), as a key regulator of hypoxic proliferative disorder of pulmonary arterial smooth muscle cells (PASMCs). Quantitative real-time PCR (qRT-PCR) analysis validated that exposure to hypoxia markedly increased the circWDR37 level in cultured human PASMCs. As evidenced by flow cytometry, 5-ethynyl-2 & PRIME;-deoxyuridine (EdU) incorporation, wound healing, and Tunel assay, silencing of endogenous circWDR37 attenuated proliferation and cell-cycle progression in hypoxia-exposed human PASMCs in vitro. Furthermore, bioinformatics and Luciferase assay showed that circWDR37 directly sponged hsa-miR-138-5p (miR-138) and was involved in the immunoregulatory and inflammatory processes of PAH. Together, these studies suggested new insights into circRNA regulated the pathology of PAH, providing a new potential therapeutic target for PAH treatment.

Automated summary

This study identified an upregulated circRNA, circWDR37, in patients with pulmonary arterial hypertension (PAH), and demonstrated its role as a key regulator of hypoxia-induced abnormal proliferation in pulmonary arterial smooth muscle cells (PASMCs). Silencing circWDR37 attenuated proliferation and cell-cycle progression in hypoxia-exposed human PASMCs, and the circRNA was found to directly interact with miR-138, implicating its involvement in the immunoregulatory and inflammatory processes of PAH. These findings provide new insights into the pathology of PAH and offer a potential therapeutic target for treatment.