Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma.
Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma.
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DOI：
10.1016/j.molcel.2010.11.020
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发表时间：
2010-12-10
期刊：
影响因子：
16
通讯作者：
Novina CD
中科院分区：
文献类型：
--
作者：
Levy C;Khaled M;Iliopoulos D;Janas MM;Schubert S;Pinner S;Chen PH;Li S;Fletcher AL;Yokoyama S;Scott KL;Garraway LA;Song JS;Granter SR;Turley SJ;Fisher DE;Novina CD
当它逃脱早期检测时，恶性黑色素瘤成为一种高致命性和治疗难治性癌症。Melastatin在转移性黑色素瘤中被大大下调，并且被广泛认为是黑色素瘤肿瘤抑制剂。在这里，我们报告说，肿瘤抑制活性不是由melastatin介导的，而是由melastatin内含子内的microRNA（miR-211）。增加miR-211而不是melastatin的表达减少了以melastatin和miR-211的低水平为特征的恶性和高度侵袭性人黑素瘤的迁移和侵袭。一个无偏的网络分析黑色素瘤表达的基因过滤其在转移中的作用，确定了三个中心节点基因：IGF 2 R，TGFBR 2和NFAT 5。这些基因的表达被miR-211降低，并且每个基因的敲低表型模仿了增加的miR-211对黑素瘤侵袭性的影响。这些数据表明miR-211是黑色素瘤侵袭的抑制因子，其表达在人黑色素瘤进展过程中通过抑制整个melastatin基因座而沉默（或被选择）。
When it escapes early detection, malignant melanoma becomes a highly-lethal and treatment-refractory cancer. Melastatin is greatly downregulated in metastatic melanomas and is widely believed to function as a melanoma tumor suppressor. Here we report that tumor suppressive activity is not mediated by melastatin but instead by a microRNA (miR-211) hosted within an intron of melastatin. Increasing expression of miR-211 but not melastatin reduced migration and invasion of malignant and highly invasive human melanomas characterized by low levels of melastatin and miR-211. An unbiased network analysis of melanoma-expressed genes filtered for their roles in metastasis identified three central node genes: IGF2R, TGFBR2, and NFAT5. Expression of these genes was reduced by miR-211 and knockdown of each gene phenocopied the effects of increased miR-211 on melanoma invasiveness. These data implicate miR-211 as a suppressor of melanoma invasion whose expression is silenced (or selected against) via suppression of the entire melastatin locus during human melanoma progression.
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影响因子：
3.3
作者：
Deeds, J;Cronin, F;Duncan, LM
通讯作者：
Duncan, LM
DOI：
10.1111/j.1600-0749.2006.00322.x
发表时间：
2006-08-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Hoek, Keith S.;Schlegel, Natalie C.;Dummer, Reinhard
通讯作者：
Dummer, Reinhard
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT
影响因子：
64.5
作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
通讯作者：
Young RA
影响因子：
4.4
作者：
Hunter, JJ;Shao, J;Shyjan, AW
通讯作者：
Shyjan, AW