Negative regulation of the tumor suppressor p53 gene by microRNAs

被引:0
作者
M Kumar
Z Lu
A A L Takwi
W Chen
N S Callander
K S Ramos
K H Young
Y Li
机构
[1] Center for Genetics and Molecular Medicine,Department of Biochemistry and Molecular Biology
[2] School of Medicine,Department of Pathology and Laboratory Medicine/Oncology
[3] University of Louisville,undefined
[4] Paul P Carbone Comprehensive Cancer Center,undefined
[5] University of Wisconsin School of Medicine and Public Health,undefined
[6] 3Current address: Department of Biotechnology,undefined
[7] Assam University,undefined
[8] Silchar-788011,undefined
[9] Assam,undefined
[10] India.,undefined
[11] 4Current address: Department of Medical Laboratory and Central Laboratory,undefined
[12] The Central Hospital of Wuhan,undefined
[13] Wuhan,undefined
[14] Hubei 430014,undefined
[15] PR China.,undefined
来源
Oncogene | 2011年 / 30卷
关键词
microRNA; p53; senescence; apoptosis; cell cycle arrest; multiple myeloma;
D O I
暂无
中图分类号
学科分类号
摘要
The tumor suppressor p53, encoded by the TP53 gene, is recognized as the guardian of the human genome because it regulates many downstream genes to exercise its function in cell cycle and cell death. Recent studies have revealed that several microRNAs (miRNAs) are important components of the p53 tumor suppressor network with miR-125b and miR-504 directly targeting TP53. In this study, we use a screening method to identify that two miRNAs (miR-25 and miR-30d) directly target the 3′UTR of TP53 to downregulate p53 protein levels and reduce the expression of genes that are transcriptionally activated by p53. Correspondingly, both miR-25 and miR-30d adversely affect apoptotic cell death, cell cycle arrest and cellular senescence. Inhibition of either miR-25 or miR-30d expression increases endogenous p53 expression and elevates cellular apoptosis in several cell lines, including one from multiple myeloma that has little TP53 mutations. Thus, beyond miR-125b and miR-504, the human TP53 gene is negatively regulated by two more miRNAs: miR-25 and miR-30d.
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页码:843 / 853
页数:10
相关论文
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