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

Abstract

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.

Single-cell transcriptomics reveals lasting changes in the lung cellular landscape into adulthood after neonatal hyperoxic exposure

“…Malat1 is ubiquitously expressed in all cells during early embryonic stages, while in adult tissues Malat1 expression varies among tissue types with high expression in the lung, brain, and pancreas [ 61 , 62 ]. Previous studies have shown that Malat1 expression is increased in peripheral blood samples from BPD patients and in rodent lungs of BPD models [ 63 , 64 ]. Malat1 was also increased in AT2 cells by neonatal hyperoxia.…”

miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

“…Nevertheless, there are still contradictions regarding the detailed roles of certain lncRNAs. Some studies showed that lncRNA MALAT1 promoted BPD induced by hyperoxia through interacting with CREB 32 . However, other studies showed that lncRNA MALAT1 protected preterm infants with BPD by inhibiting cell apoptosis 33 .…”

The Trinity of cGAS, TLR9, and ALRs Guardians of the Cellular Galaxy Against Host-Derived Self-DNA

“…STING activation also plays a crucial role in bronchopulmonary dysplasia (BPD) in preterm infants (a lung inflammatory conditions induced due to hyperoxia) due to an increase in the long-non coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) that interacts with the cAMP response element-binding protein (CREB) to increase its transcription ( 128 ). MALAT1 increases HMGB1 concentration that may further activate cGAS-STING signaling by increasing the curvature of dsDNA that increases its binding potential to cGAS ( 129 ).…”