Long non-coding RNA and microRNA-675/let-7a mediates the protective effect of melatonin against early brain injury after subarachnoid hemorrhage via targeting TP53 and neural growth factor

作者：Song Yang, Wanzhong Tang, Yuchao He, Linbao Wen, Bin Sun, Shengli Li · 发表于：Cell Death and Disease · 年份：2018 · DOI：10.1038/s41419-017-0155-8 · 被引用次数：66 · 研究领域：Neurogenesis and neuroplasticity mechanisms、MicroRNA in disease regulation、Cancer-related molecular mechanisms research

Abstract The objective of this study was to identify the protective effect of melatonin (MT) against early brain injury (EBI) following subarachnoid hemorrhage (SAH) and explore the underlying molecular mechanism. Real-time polymerase chain reaction (PCR) and luciferase assay were utilized to detect the effect of MT on H19 expression level, computation analysis and luciferase assay were conducted to the underlying mechanism of let-7a and miR-675. Real-time PCR, western blot analysis, immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry analysis were performed to detect the effect of MT on H19, miR-675, let-7a, TP53, neural growth factor (NGF) levels, cell viability, and apoptosis status. Melatonin increased H19 expression level by enhancing H19 transcriptional efficiency in a concentration-dependent manner. MiR-675 and let-7a directly targeted P53 and NGF, respectively, and miR-675 reduced luciferase activity of wild-type but not mutant TP53 3′UTR. Meanwhile, let-7a suppressed luciferase activity of wild-type but not mutant NGF 3′UTR. H 2 O 2 increased number of SA-b-gal, and while MT administration repressed the premature senescence. H 2 O 2 obviously upregulated expressions of H19, miR-675, and NGF, and downregulated let-7a and TP53 levels; however, MT treatment reduced expressions of H19, miR-675, and NGF, and improved let-7a and TP53 levels. Treating with MT attenuated the neurological deficits and reduced the ...