Neonatal respiratory distress syndrome (NRDS) is a leading cause of morbidity in premature newborns and is a common reason for admission to the neonatal intensive care unit (NICU). Recent studies found that the pathogenesis of NRDS is not simply lung immaturity. Apoptosis is an essential process for the development and maturation of the lungs. In this study, we report a critical role of lncRNA MALAT1 in regulating CD80 transcription in the NRDS-associated apoptosis via binding with NF-κB. We first showed MALAT1 and CD80 were highly expressed in the peripheral blood mononuclear cells of NRDS with infection exposure. Then we found MALAT1 expressions were significantly increased by the treatment of LPS. We confirmed knockdown of MALAT1 promoted cell viability by CCK-8 assays, cell apoptosis by flow cytometric assays and cytoskeleton destruction by immunocytochemistry. We confirmed CD80 expression level was associated with cell apoptosis by affecting PARP and caspase-3. Then we demonstrated knockdown of MALAT1 promoted CD80 transcription in A549 cells. Furthermore, we confirmed that MALAT1 downregulated transcriptional expression of CD80 by interfering with NF-κB activation and disrupting its binding efficiency with the CD80 promoter in the cell nucleus. In conclusion, we first identified lncRNA MALAT1 as an important prognosis maker for NRDS patients. Most significantly, this study then demonstrated a novel regulatory function of knocked-down MALAT1 on the transcriptional level of CD80 by enhancing the binding of NF-κB to CD80 promoter. Since the interaction between MALAT1 and CD80 plays an essential role in the cell apoptosis of NRDS, our findings demonstrate the possibility of using MALAT1 as therapeutic target for treatment of NRDS, and extend existing knowledge about the molecular mechanism that underlies NRDS pathogensis.
Keywords: CD80; LncRNA MALAT1; NF-κB; Neonatal respiratory distress syndrome (NRDS); Transcriptional regulation.
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