LncRNA CASC2 targets CAV1 by competitively binding with microRNA-194-5p to inhibit neonatal lung injury.

Abstract

Long non-coding RNAs (lncRNAs) are vital regulators of different biological processes during bronchopulmonary dysplasia (BPD). This study was conducted to probe the biological roles of lncRNA CASC2 in the pathogenesis of BPD and neonatal lung injury. Firstly, a hyperoxia-induced mouse model with BPD was established. LncRNAs with differential expression in lung tissues of normal and BPD mice were analyzed by microarray. An adenovirus vector overexpressing CASC2 was constructed and its functions on BPD symptoms in model mice were analyzed. Gain- and loss-of function studies of CASC2 were performed in a bronchial epithelial cell line BEAS-2B to determine its role in cell apoptosis and proliferation under normoxic and hyperoxic conditions. The downstream mechanical molecules of lncRNA CASC2 were predicted on bioinformatics systems and confirmed by luciferase assays. The functional interactions among lncRNA CASC2, miR-194-5p, and CAV1 in BPD were determined by rescue experiments. Consequently, lncRNA CASC2 was found to be poorly expressed in BPD mice. Besides, overexpressed CASC2 was found to relieve the symptoms of BPD in neonatal mice and suppress apoptosis as well as promote proliferation in hyperoxia-induced BEAS-2B cells. Importantly, CASC2 was found to regulate CAV1 expression by competitively binding to miR-194-5p and downregulate the activity of the TGF-β1 signaling pathway, thereby suppressing lung injury. Either miR-194-5p upregulation or CAV1 downregulation blocked the roles of CASC2. To sum up, this study evidenced that CASC2 alleviates hyperoxia-induced lung injury in mouse and cell models with the involvement of a miR-194-5p-CAV1 crosstalk and the TGF-β1 inactivation.

• Authors: Lili Ji, Zunjie Liu, Chengya Dong, Dongping Wu, Shimei Yang, Limei Wu
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 118 Pg. 104575 (02 2021) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 33212124 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cav1 protein, mouse
• Caveolin 1
• MIRN194 microRNA, mouse
• MicroRNAs
• RNA, Long Noncoding

Topics

• Animals
• Animals, Newborn
• Apoptosis
• Caveolin 1 (antagonists & inhibitors, genetics, metabolism)
• Cell Proliferation
• Female
• Gene Expression Regulation
• Hyperoxia (physiopathology)
• Lung Injury (etiology, metabolism, pathology, prevention & control)
• Male
• Mice
• MicroRNAs (genetics, metabolism)
• RNA, Long Noncoding (genetics)
• Signal Transduction