@article{87c4768e9cfc4828aaf7f72a0b2679ca,
title = "Intronic miR-211 Assumes the Tumor Suppressive Function of Its Host Gene in Melanoma",
abstract = "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.",
author = "Carmit Levy and Mehdi Khaled and Dimitrios Iliopoulos and Janas, {Maja M.} and Steffen Schubert and Sophie Pinner and Chen, {Po Hao} and Shuqiang Li and Fletcher, {Anne L.} and Satoru Yokoyama and Scott, {Kenneth L.} and Garraway, {Levi A.} and Song, {Jun S.} and Granter, {Scott R.} and Turley, {Shannon J.} and Fisher, {David E.} and Novina, {Carl D.}",
note = "Funding Information: We would like to gratefully acknowledge Dr. Meenhard Herlyn for supplying several melanoma short-term cultures for these studies. We also wish to thank Dr. Andrew Kung and Dr. Hans Wildund for insightful discussions. This work was funded by National Institutes of Health (NIH) grant AR043369 (D.E.F.), the Melanoma Research Alliance (D.E.F), the Adelson Medical Research Foundation (D.E.F.), The US-Israel Binational Science Foundation (D.E.F.), the Doris Duke Medical Foundation (D.E.F.), the Doris Duke Medical Foundation (C.D.N.), and by American Cancer Society (C.D.N.). S.L. was supported by NRSA Fellowship (NIH/NCI T32 CA070083). ",
year = "2010",
month = dec,
day = "10",
doi = "10.1016/j.molcel.2010.11.020",
language = "英語",
volume = "40",
pages = "841--849",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}
