دورية أكاديمية
أعرض في EDS

PVT1 dependence in cancer with MYC copy-number increase.

التفاصيل البيبلوغرافية
العنوان: PVT1 dependence in cancer with MYC copy-number increase.
المؤلفون: Tseng YY; Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Moriarity BS; 1] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2]., Gong W; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [3]., Akiyama R; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Tiwari A; 1] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Center for Bio-Design, Translational Health Science and Technology Institute, Gurgaon 122016, India., Kawakami H; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Ronning P; Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Reuland B; Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Guenther K; Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Beadnell TC; Department of Laboratory Medicine and Pathology, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Essig J; Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Otto GM; Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., O'Sullivan MG; Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Largaespada DA; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA., Schwertfeger KL; 1] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Department of Laboratory Medicine and Pathology, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [3]., Marahrens Y; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2]., Kawakami Y; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [3]., Bagchi A; 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA.
المصدر: Nature [Nature] 2014 Aug 07; Vol. 512 (7512), pp. 82-6. Date of Electronic Publication: 2014 Jun 22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: DNA Copy Number Variations/*genetics , Gene Amplification/*genetics , Gene Dosage/*genetics , Genes, myc/*genetics , Oncogene Protein p55(v-myc)/*genetics , RNA, Long Noncoding/*genetics, Animals ; Cell Transformation, Neoplastic ; Chromosomes, Human, Pair 8/genetics ; Disease Models, Animal ; HCT116 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Oncogene Protein p55(v-myc)/metabolism ; Phenotype
مستخلص: 'Gain' of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers and is associated with poor prognosis. The well-characterized myelocytomatosis (MYC) oncogene resides in the 8q24.21 region and is consistently co-gained with an adjacent 'gene desert' of approximately 2 megabases that contains the long non-coding RNA gene PVT1, the CCDC26 gene candidate and the GSDMC gene. Whether low copy-number gain of one or more of these genes drives neoplasia is not known. Here we use chromosome engineering in mice to show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsdmc fails to advance cancer measurably, whereas a single supernumerary segment encompassing all four genes successfully promotes cancer. Gain of PVT1 long non-coding RNA expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumours, and copy number of PVT1 was co-increased in more than 98% of MYC-copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency. As MYC protein has been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 long non-coding RNA provides a much needed therapeutic target.
التعليقات: Comment in: Cell Res. 2014 Nov;24(11):1284-5. (PMID: 25104732)
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معلومات مُعتمدة: P30 CA077598 United States CA NCI NIH HHS; R01 AR064195 United States AR NIAMS NIH HHS
المشرفين على المادة: 0 (Oncogene Protein p55(v-myc))
0 (PVT1 long-non-coding RNA, human)
0 (RNA, Long Noncoding)
تواريخ الأحداث: Date Created: 20140722 Date Completed: 20140929 Latest Revision: 20220408
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4767149
DOI: 10.1038/nature13311
PMID: 25043044
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/nature13311