Downregulation of UNC5B-AS1 in Preterm Infants with Bronchopulmonary Dysplasia and Its Protective Mechanism via the miR-134-5p/IGF1 Axis.

PURPOSE: Bronchopulmonary dysplasia (BPD) is a major chronic lung disease in preterm infants. This study was designed to elucidate the functional significance and molecular mechanism of the long non-coding RNA UNC5B-AS1 in BPD pathogenesis. CLINICAL SAMPLES AND CELL ASSAYS: This study included 50 preterm infants with BPD and 42 healthy newborns. The levels of UNC5B-AS1, miR-134-5p, IGF1, Bax, and Bcl-2 were detected by RT-qPCR. In in vitro experiments, A549 and MLE-12 cells were used to establish a hyperoxia-induced BPD model. A series of assays was performed to evaluate the cellular phenotypes, including CCK-8 for viability, flow cytometry for apoptosis, ELISA for inflammatory factors (TNF-α, IL-1β, IL-6), and SOD activity, and DCFH-DA probing for ROS levels. IGF1 protein expression was examined by Western blot. Dual-luciferase reporter assay and RIP experiments were performed to validate the targeting relationships between UNC5B-AS1 and miR-134-5p, and between miR-134-5p and IGF1. RESULTS: Serum levels of UNC5B-AS1 were significantly downregulated, while miR-134-5p expression was significantly upregulated in BPD infants, both showing good diagnostic value. UNC5B-AS1 directly binds to miR-134-5p. In the cellular model, the protective effect of UNC5B-AS1 overexpression against hyperoxia-induced injury was reversed by miR-134-5p overexpression. Furthermore, IGF1 was confirmed as a direct target of miR‑134‑5p, and knockdown of IGF1 abolished the protective effects achieved by miR‑134‑5p inhibition. CONCLUSION: Serum UNC5B‑AS1 is downregulated and miR‑134‑5p is upregulated in preterm BPD infants. Mechanistically, UNC5B‑AS1 may sponges miR‑134‑5p to upregulate IGF1, protecting against hyperoxia‑induced alveolar injury.