Intronic miR-211 Assumes the Tumor Suppressive Function of Its Host Gene in Melanoma

被引：234

作者：

Levy, Carmit ^{[1
]}

Khaled, Mehdi ^{[1
,2
,7
,8
]}

Iliopoulos, Dimitrios ^{[4
]}

Janas, Maja M. ^{[2
,7
,8
]}

Schubert, Steffen ^{[2
,7
,8
]}

Pinner, Sophie ^{[2
]}

Chen, Po-Hao ^{[2
,7
,8
]}

Li, Shuqiang ^{[2
,7
,8
]}

Fletcher, Anne L. ^{[2
]}

Yokoyama, Satoru ^{[1
]}

Scott, Kenneth L.

Garraway, Levi A. ^{[3
,7
,8
]}

Song, Jun S. ^{[6
]}

Granter, Scott R. ^{[5
]}

Turley, Shannon J. ^{[2
]}

Fisher, David E. ^{[1
]}

Novina, Carl D. ^{[2
,7
,8
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA

[2] Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[6] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[7] Broad Inst Harvard, Cambridge, MA 02141 USA

[8] MIT, Cambridge, MA 02141 USA

来源：

MOLECULAR CELL | 2010年 / 40卷 / 05期

基金：

美国国家卫生研究院;

关键词：

BREAST-CANCER; MALIGNANT-MELANOMA; MASTER REGULATOR; IN-VIVO; EXPRESSION; MICRORNAS; METASTASIS; CELLS; MITF; PROGNOSIS;

D O I：

10.1016/j.molcel.2010.11.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：841 / 849

页数：9

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