Long Non-coding RNA TUG1 Modulates Expression of Elastin to Relieve Bronchopulmonary Dysplasia via Sponging miR-29a-3p

Abstract

Objective: Multiple studies have highlighted that long non-coding RNAs (lncRNAs) may exert paramount roles in relieving bronchopulmonary dysplasia (BPD). The aim of our investigation is to probe the role and mechanism of lncRNA taurine upregulated gene 1 (TUG1) in BPD. Methods:The current mouse model of BPD was simulated by induction of hyperoxia, and hyperoxia-induced mouse type II alveolar epithelial (MLE-12) (MLE-12) cells were established as a cellular model. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine relative expressions of TUG1, miR-29a-3p, and elastin (ELN). We assessed cell apoptosis by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. Western blot was used for detection of apoptosis-related proteins. Moreover, cell viability was tested by cell counting kit-8 (CCK-8) assay. Inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter (DLR) assay was employed to confirm relationship between genes.Results: Upregulation of miR-29a-3p was found in lung tissues of BPD mice compared with lung tissues without BPD, while downregulations of TUG1 and ELN were discovered in BPD tissues in comparison with tissues without BPD. Increasing TUG1 was shown to alleviate lung injury of BPD mice and promote proliferation of hyperoxia-induced MLE-12 cells. Meanwhile, TUG1 inhibited inflammatory response and cell apoptosis in lung tissues of BPD mice and hyperoxia-induced MLE-12 cells. miR-29a-3p was targeted by TUG1 and negatively modulated by TUG1. ELN was inversely regulated by miR-29a-3p. Meantime, suppressive effects of TUG1 on apoptosis and inflammation were reversed by decreasing ELN or increasing miR-29a-3p in hyperoxia-induced MLE-12 cells.Conclusion: lncRNA TUG1 relieved BPD through regulating the miR-29a-3p/ELN axis, which provided a therapeutic option to prevent or ameliorate BPD.

Circular RNAs expression profiles and bioinformatics analysis in bronchopulmonary dysplasia

“…With the mounting discovery of several non‐coding RNAs, including miRNAs, lncRNAs, and circRNAs, more spotlights have been focused on exploring their relationship with BPD. Recent data show that circRNAs and the downstream target genes play crucial roles in various biological processes associated with damage repair after immaturity lung injury 7,33,34 . Therefore, it is essential to investigate the interactions and regulatory mechanisms of the ceRNA network in the development and progression of BPD.…”

“…Recent data show that circRNAs and the downstream target genes play crucial roles in various biological processes associated with damage repair after immaturity lung injury. 7,33,34 To elucidate the molecular processes and pathways that underlie complex diseases, ceRNA regulation network analysis is a powerful approach. A recent study revealed that in the LPS-induced lung injury model, circRNA was functional as miRNA sponges that interacted with hsa-miR-4688 and hsa-miR-3192-5p in the inflammation process of Human bronchial epithelial (BEAS-2B) cell damage.…”

Characterization of the microRNA Transcriptomes and Proteomics of Cochlea Tissue-derived Small Extracellular Vesicles From Different Age of Mice After Birth

“…miR29a-3p, miR449a-5p, and miR147-3p have been reported to be accumulated in exosomes derived from oral squamous cells, macrophages, and bronchoalveolar lavage uid [53,55,96,97]. In addition, upregulation of miR29a-3p rescues bronchopulmonary dysplasia and has a negative regulatory effect on the Smad, NFκB, and canonical Wnt signaling pathways [98][99][100]. Importantly, miR29a-3p directly targets the Wnt-related genes DVL3 (Dishevelled 3), CSNK2A2 (casein kinase 2 alpha 2 polypeptide), FZD3 (Frizzled family receptor 3), and FZD5 (Frizzled family receptor 5) [100].…”

Microbial and metabolic profiles of bronchopulmonary dysplasia and therapeutic effects of potential probiotics Limosilactobacillus reuteri and Bifidobacterium bifidum

“…Mouse alveolar epithelial cells MLE‐12 were purchased from American Type Culture Collection (ATCC) and cultured in RPMI‐1640 medium with 10% foetal calf serum (FCS) and penicillin/streptomycin (100 U ml −1 ). They were then incubated in a 5% CO 2 incubator at 37°C (Zhong et al, 2020). Next, the cells were inoculated in a six‐well plate and cultured for 24 h. After exposure to the medium supplemented with 0.1% FCS for 6 h, the cells were kept in indoor air (21% O 2 ) or hyper oxygen (85% O 2 ) for 6 h (Chen et al, 2017; Chen et al, 2019).…”