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

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.

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.

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.

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.