MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene

	MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene
	Lu, Z; Liu, M; Stribinskis, V; Klinge, CM; Ramos, KS; Colburn, NH; Li, Y
刊名	ONCOGENE
	2008
卷号	27 期号:31 页码:4373-4379
关键词	miR-21 PDCD4 cell transformation microRNA tumor suppressor
通讯作者	Li, Y (reprint author), Univ Louisville, Dept Biochem & Mol Biol, 319 Abraham Flexner Way,Rm 513-A Building, Louisville, KY 40202 USA.,yong.li@louisville.edu
英文摘要	MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively control expression of target genes in animals and plants. The microRNA-21 gene (mir-21) has been identified as the only miRNA commonly over-expressed in solid tumors of the lung, breast, stomach, prostate, colon, brain, head and neck, esophagus and pancreas. We initiated a screen to identify miR-21 target genes using a reporter assay and identified a potential miR-21 target in the 30-UTR of the programmed cell death 4 (PDCD4) gene. We cloned the full-length 30-UTR of human PDCD4 downstream of a reporter and found that mir-21 downregulated, whereas a modified antisense RNA to miR-21 upregulated report er activity. Moreover, deletion of the putative miR-21-binding site (miRNA regulatory element, MRE) from the 30-UTR of PDCD4, or mutations in the MRE abolished the ability of miR-21 to inhibit reporter activity, indicating that this MRE is a critical regulatory region. Western blotting showed that Pdcd4 protein levels were reduced by miR-21 in human and mouse cells, whereas quantitative real-time PCR revealed little difference at the mRNA level, suggesting translational regulation. Finally, overexpression of mir-21 in MCF-7 human breast cancer cells and mouse epidermal JB6 cells promoted soft agar colony formation by downregulating Pdcd4 protein levels. The demonstration that miR-21 promotes cell transformation supports the concept that mir-21 functions as an oncogene by a mechanism that involves translational repression of the tumor suppressor Pdcd4.
学科主题	Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity
类目[WOS]	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]	TUMOR-SUPPRESSOR GENE ; INITIATION-FACTOR 4A ; BREAST-CANCER ; MICRO-RNA ; EXPRESSION ; PDCD4 ; TRANSLATION ; SIGNATURE ; BINDING ; PROGRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000257691100012
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1477]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Lu, Z,Liu, M,Stribinskis, V,et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene[J]. ONCOGENE,2008,27(31):4373-4379.
APA	Lu, Z.,Liu, M.,Stribinskis, V.,Klinge, CM.,Ramos, KS.,...&Li, Y.(2008).MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene.ONCOGENE,27(31),4373-4379.
MLA	Lu, Z,et al."MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene".ONCOGENE 27.31(2008):4373-4379.