MicroRNA-4279 Inhibits Cell Apoptosis through Upregulating Notch-1 Expression by Targeting the Core Promoter Region[J]. Journal of Sun Yat-sen University (Medical Sciences), 2015, 36(5).
MicroRNA-4279 Inhibits Cell Apoptosis through Upregulating Notch-1 Expression by Targeting the Core Promoter Region[J]. Journal of Sun Yat-sen University (Medical Sciences), 2015, 36(5).DOI:
Abstract: 【Objective】 To investigate the regulation of Notch-1 expression by miRNAs through targeting the core promoter region and get insight into the role of miRNA mediated transcriptional regulation in the carcinogenesis of the lymphocytes. 【Method】 First
miRNA binding sites in the core promoter region of Notch-1 gene were predicted. Then the dual-luciferase assay was conducted to determine whether the miRNA(s) could induce Notch-1 promoter activation. Furthermore
mutations were introduced to the putative binding site of the miRNA in Notch-1 promoter to confirm the target site of miRNA. Next
RT-qPCR and Western Blot assay were used to determine whether the miRNA could modulate the endogenous mRNA and protein expression of Notch-1 gene. Then we transfected miRNA into H9 cell and determined its effect on cell apoptosis under the condition of H2O2 treatment. By knocking down Notch-1
we further determined whether the miRNA induced anti-apoptosis is dependent of the Notch-1 pathway. 【Results】 We found that miR-4279 had a putative binding site on the core promoter region of Notch-1 gene; and miR-4279 could increase the promoter activity of Notch-1. Furthermore
mutation assay suggests that this site is the actual target of miR-4279 for promoter activation. Overexpressing miR-4279 significantly increased Notch-1 mRNA and protein expressions in H9 cells. Moreover
miR-4279 could readily inhibit H9 cells’ apoptosis induced by H2O2. The knock-down assay of Notch-1 showed that the miR-4279 induced anti-apoptosis effect is dependent on the Notch-1 signaling pathway. 【Conclusion】 MiR-4279 upregulates Notch-1 gene expression through targeting the core promoter region
which confers the anti-apoptosis ability to lymphocytes.