کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2817211 | 1159975 | 2013 | 5 صفحه PDF | دانلود رایگان |
• This paper found that 1,25-(OH)2VD3 up-regulates hsa-let-7a-2 gene expression.
• This paper studied regulatory mechanisms of hsa-let-7a-2 expression.
• Up-regulation of hsa-let-7a-2 expression mediated anti-proliferation effects
AimsWe aim to investigate the relationship between 1,25-(OH)2VD3 and hsa-let-7a in lung cancer A549 cells.MethodsReal-time PCR and luciferase reporter assays were used to detect the influence of 1,25-(OH)2VD3 on the expression of hsa-let-7a-2 after A549 cells were treated with 1,25-(OH)2VD3 (10− 8 ~ 10− 6 mol/L). Analysis of the 5.0 Kb upstream sequence of the pre-let-7a-2 showed that one vitamin D response element (VDRE) is located in -2066/-2042 bp of pre-let-7a-2. Electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to determine whether 1,25-(OH)2VD3 activating vitamin D receptor (VDR) could bind to this VDRE to promote hsa-let-7a-2 expression.ResultsWe found that 1,25-(OH)2VD3 could up-regulate the expression of hsa-let-7a-2 in a dose-dependent manner. The results of EMSA and ChIP demonstrated that 1,25-(OH)2VD3/VDR could interact with the VDRE in the upstream of pre-let-7a-2. Luciferase reporter assay showed that this VDRE is a functional cis-element mediating the up-regulation of hsa-let-7a-2 expression induced by 1,25-(OH)2VD3.ConclusionsOur data indicated that 1,25-(OH)2VD3 could up-regulate the transcription of hsa-let-7a-2 in lung cancer cells, and the up-regulation of hsa-let-7a-2 expression induced by 1,25-(OH)2VD3 might mediate the anti-proliferation effects of 1,25-(OH)2VD3 in lung cancer cells.
Journal: Gene - Volume 522, Issue 2, 15 June 2013, Pages 142–146