Long non‐coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 18; pp. 10478 - 10492
• Main Authors: Chen, Jia‐He, Feng, Dan‐Dan, Chen, Yu‐Fei, Yang, Cai‐Xia, Juan, Chen‐Xia, Cao, Qian, Chen, Xi, Liu, Shuang, Zhou, Guo‐Ping
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2020; John Wiley and Sons Inc
• Subjects: Animal models; Animals; Antibodies; Apoptosis; Apoptosis - genetics; Binding sites; Bronchopulmonary dysplasia (BPD); Bronchopulmonary Dysplasia - blood; Bronchopulmonary Dysplasia - genetics; cAMP response element–binding protein (CREB); Cell culture; Cell Line; Cell lines; Cell proliferation; Cell Proliferation - genetics; Chromatin; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Deoxyribonucleic acid; DNA; Dysplasia; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Flow cytometry; Gene expression; Gene Expression Regulation; Gene Silencing; Humans; Hyperoxia; Hyperoxia - genetics; Immunoprecipitation; Infant, Newborn; Infants; Inflammation; Interferon; Leukocytes, Mononuclear - metabolism; Lung - metabolism; Lung - pathology; Lung cancer; Lung diseases; Male; Medical research; Membrane Proteins - blood; Membrane Proteins - genetics; Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1); Models, Biological; Neonates; Non-coding RNA; Original; Pathogenesis; Phosphorylation; Plasmids; Promoter Regions, Genetic - genetics; Proteins; Rats; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Stimulator of interferon genes (STING); Therapeutic targets; Transcription, Genetic; Up-Regulation - genetics; Western blotting; United Kingdom > UK; United States > US; China; Japan; Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1); cAMP response element-binding protein (CREB); Stimulator of interferon genes (STING); Bronchopulmonary dysplasia (BPD)
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15661

Bronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non‐coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up‐regulated in the lung tissue from BPD neonates, hyperoxia‐based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down‐regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia‐treated cells. Subsequently, qRT‐PCR, Western blotting and dual‐luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.