miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death.
miR-1226 targets expression of the mucin 1 oncoprotein and induces cell death.
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DOI：
10.3892/ijo_00000653
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发表时间：
2010-07
影响因子：
5.2
通讯作者：
Kufe D
中科院分区：
文献类型：
--
作者：
Jin C;Rajabi H;Kufe D
MUC1癌蛋白在人类肿瘤和血液恶性肿瘤中异常过表达。MicroRNAs （miRNAs）与肿瘤发生的抑制和诱导有关。目前的研究表明，MUC1 mRNA 3 ‘非翻译区（3 ’ utr）包含一个高度保守的基序，用于结合一种未知靶点的新型miRNA miR-1226。结果表明，miR-1226在人乳腺癌细胞系和非恶性乳腺上皮细胞中均有表达。我们还发现miR-1226与MUC1 mRNA 3'UTR相互作用，miR-1226下调内源性MUC1蛋白水平。与miR-1226诱导MUC1表达下调一致，结果表明miR-1226诱导(i)活性氧增加，（ii）线粒体跨膜电位丧失，以及（iii）细胞存活率降低。这些发现表明，miR-1226下调MUC1癌蛋白的表达，miR-1226因此通过促进诱导细胞死亡而发挥肿瘤抑制作用。
The MUC1 oncoprotein is aberrantly overexpressed in human carcinomas and hematologic malignancies. MicroRNAs (miRNAs) have been implicated in the suppression and induction of oncogenesis. The present studies demonstrate that the MUC1 mRNA 3′ untranslated region (3′UTR) contains a highly conserved motif for binding of a novel miRNA, miR-1226, that has no known targets. The results show that miR-1226 is expressed in human breast cancer cell lines and non-malignant mammary epithelial cells. We also show that miR-1226 interacts with the MUC1 mRNA 3′UTR and that miR-1226 downregulates endogenous MUC1 protein levels. Consistent with miR-1226-induced downregulation of MUC1 expression, the results demonstrate that miR-1226 induces (i) an increase in reactive oxygen species, (ii) loss of the mitochondrial transmembrane potential, and (iii) a decrease in cell survival. These findings indicate that expression of the MUC1 oncoprotein is downregulated by miR-1226 and that miR-1226 thereby functions as a tumor suppressor by promoting the induction of cell death.
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MUC1癌蛋白通过抑制caspase-8的募集来阻断死亡受体介导的凋亡。
影响因子：
11.2
作者：
Agata, Naoki;Ahmad, Rehan;Kawano, Takeshi;Raina, Deepak;Kharbanda, Surender;Kufe, Donald
通讯作者：
Kufe, Donald
影响因子：
4.8
作者：
Gaemers, IC;Vos, HL;Hilkens, J
通讯作者：
Hilkens, J
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
8
作者：
Mott, J. L.;Kobayashi, S.;Gores, G. J.
通讯作者：
Gores, G. J.