Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis
文献类型:期刊论文
作者 | Ma, XD; Kumar, M; Choudhury, SN; Buscaglia, LEB; Barker, JR; Kanakamedala, K; Liu, MF; Li, Y |
刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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出版日期 | 2011 |
卷号 | 108期号:25页码:10144-10149 |
关键词 | microRNA chemical-induced carcinogenesis Ras effector pathways |
通讯作者 | Li, Y (reprint author), Univ Louisville, Sch Med, Dept Biochem & Mol Biol, 319 Abraham Flexner Way, Louisville, KY 40202 USA.,yong.li@louisville.edu |
英文摘要 | MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies. To determine whether miR-21 promotes tumor development in vivo, we knocked out the miR-21 allele in mice. In response to the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate mouse skin carcinogenesis protocol, miR-21-null mice showed a significant reduction in papilloma formation compared with wild-type mice. We revealed that cellular apoptosis was elevated and cell proliferation was decreased in mice deficient of miR-21 compared to wild-type animals. In addition, we found that a large number of validated or predicted miR-21 target genes were up-regulated in miR-21-null keratinocytes, which are precursor cells to skin papillomas. Specifically, up-regulation of Spry1, Pten, and Pdcd4 when miR-21 was ablated coincided with reduced phosphorylation of ERK, AKT, and JNK, three major downstream effectors of Ras activation that plays a predominant role in DMBA-initiated skin carcinogenesis. These results provide in vivo evidence that miR-21 exerts its oncogenic function through negatively regulating its target genes. |
学科主题 | Science & Technology - Other Topics |
类目[WOS] | Multidisciplinary Sciences |
关键词[WOS] | B-CELL LYMPHOMA ; SKIN CARCINOGENESIS ; SUPPRESSOR PDCD4 ; RAS ; MICRORNA-21 ; CANCER ; GROWTH ; MICE ; IDENTIFICATION ; TRANSFORMATION |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000291857500029 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/884] ![]() |
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 | Ma, XD,Kumar, M,Choudhury, SN,et al. Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2011,108(25):10144-10149. |
APA | Ma, XD.,Kumar, M.,Choudhury, SN.,Buscaglia, LEB.,Barker, JR.,...&Li, Y.(2011).Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,108(25),10144-10149. |
MLA | Ma, XD,et al."Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.25(2011):10144-10149. |
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