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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2009-9-8
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pubmed:abstractText |
The hypoxia-inducible factor (HIF) pathway is essential for cell survival under low oxygen and plays an important role in tumor cell homeostasis. We investigated the function of miR-210, the most prominent microRNA upregulated by hypoxia and a direct transcriptional target of HIFs. miR-210 expression was elevated in multiple cancer types and correlated with metastasis of breast and melanoma tumors. miR-210 overexpression in cancer cell lines bypassed hypoxia-induced cell cycle arrest and partially reversed the hypoxic gene expression signature. We identified MNT, a known MYC antagonist, as a miR-210 target. MNT mRNA contains multiple miR-210 binding sites in the 3' UTR and its knockdown phenocopied miR-210 overexpression. Furthermore, loss of MYC abolished miR-210-mediated override of hypoxia-induced cell cycle arrest. Comparison of miR-210 and MYC overexpression with MNT knockdown signatures also indicated that miR-210 triggered a "MYC-like" transcriptional response. Thus, miR-210 influences the hypoxia response in tumor cells through targeting a key transcriptional repressor of the MYC-MAX network.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN210 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MNT protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/endothelial PAS domain-containing...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1551-4005
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pubmed:author |
pubmed-author:BartzSteven RSR,
pubmed-author:BurchardJuljaJ,
pubmed-author:CarletonMichaelM,
pubmed-author:ChangAaron NAN,
pubmed-author:ClearyMichele AMA,
pubmed-author:DaiHongyueH,
pubmed-author:DaiXudongX,
pubmed-author:DiazRobert LRL,
pubmed-author:GrandoriCarlaC,
pubmed-author:HarhJ YJY,
pubmed-author:ImakuraMakiM,
pubmed-author:LinsleyPeter SPS,
pubmed-author:MarszalekJoseph RJR,
pubmed-author:SchelterJanellJ,
pubmed-author:WalshRyan MRM,
pubmed-author:ZhangZhanZ
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2756-68
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pubmed:meshHeading |
pubmed-meshheading:19652553-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:19652553-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:19652553-Binding Sites,
pubmed-meshheading:19652553-Cell Cycle,
pubmed-meshheading:19652553-Cell Hypoxia,
pubmed-meshheading:19652553-Cell Line, Tumor,
pubmed-meshheading:19652553-Cluster Analysis,
pubmed-meshheading:19652553-Gene Knockdown Techniques,
pubmed-meshheading:19652553-Humans,
pubmed-meshheading:19652553-Hypoxia-Inducible Factor 1,
pubmed-meshheading:19652553-MicroRNAs,
pubmed-meshheading:19652553-Models, Biological,
pubmed-meshheading:19652553-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:19652553-RNA, Small Interfering,
pubmed-meshheading:19652553-Repressor Proteins,
pubmed-meshheading:19652553-Up-Regulation
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pubmed:year |
2009
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pubmed:articleTitle |
MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT.
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pubmed:affiliation |
Rosetta Inpharmatics LLC, Seattle, WA, USA. microRNA210@yahoo.com
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pubmed:publicationType |
Journal Article
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