Open AccessJournal Article
Widespread microRNA repression by Myc contributes to tumorigenesis
Tsung Cheng Chang,Duonan Yu,Yun-Sil Lee,Erik A. Wentzel,Dan E. Arking,Kristin M. West,Chi V. Dang,Andrei Thomas-Tikhonenko,Joshua T. Mendell +8 more
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TLDR
It is shown here that Myc regulates a much broader set of miRNAs than previously anticipated, and extensive reprogramming of the miRNA transcriptome by Myc contributes to tumorigenesis.Abstract:
The c-Myc oncogenic transcription factor (Myc) is pathologically activated in many human malignancies. Myc is known to directly upregulate a pro-tumorigenic group of microRNAs (miRNAs) known as the miR-17-92 cluster. Through the analysis of human and mouse models of B cell lymphoma, we show here that Myc regulates a much broader set of miRNAs than previously anticipated. Unexpectedly, the predominant consequence of activation of Myc is widespread repression of miRNA expression. Chromatin immunoprecipitation reveals that much of this repression is likely to be a direct result of Myc binding to miRNA promoters. We further show that enforced expression of repressed miRNAs diminishes the tumorigenic potential of lymphoma cells. These results demonstrate that extensive reprogramming of the miRNA transcriptome by Myc contributes to tumorigenesis.read more
Citations
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The widespread regulation of microRNA biogenesis, function and decay.
TL;DR: This work has shown that the regulation of miRNA metabolism and function by a range of mechanisms involving numerous protein–protein and protein–RNA interactions has an important role in the context-specific functions of miRNAs.
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Biogenesis of small RNAs in animals.
TL;DR: This Review summarizes the current knowledge of how these intriguing molecules are generated in animal cells.
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MYC on the Path to Cancer
TL;DR: The richness of the understanding of MYC is reviewed, highlighting new biological insights and opportunities for cancer therapies.
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MicroRNAs in cancer.
TL;DR: In this paper, the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies are discussed.
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Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model
Janaiah Kota,Raghu R. Chivukula,Kathryn A. O'Donnell,Erik A. Wentzel,Chrystal L. Montgomery,Hun-Way Hwang,Tsung Cheng Chang,Perumal Vivekanandan,Michael Torbenson,K. Reed Clark,K. Reed Clark,Jerry R. Mendell,Jerry R. Mendell,Joshua T. Mendell +13 more
TL;DR: It is demonstrated that hepatocellular carcinoma (HCC) cells exhibit reduced expression of miR-26a, a miRNA that is normally expressed at high levels in diverse tissues that may provide a general strategy for miRNA replacement therapies.
References
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MicroRNA expression profiles classify human cancers
Jun Lu,Gad Getz,Eric A. Miska,Eric A. Miska,Ezequiel Alvarez-Saavedra,Justin Lamb,David Peck,Alejandro Sweet-Cordero,Alejandro Sweet-Cordero,Benjamin L. Ebert,Benjamin L. Ebert,Raymond H. Mak,Raymond H. Mak,Adolfo A. Ferrando,James R. Downing,Tyler Jacks,H. Robert Horvitz,H. Robert Horvitz,Todd R. Golub,Todd R. Golub,Todd R. Golub +20 more
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Journal Article
MicroRNA signatures in human cancers
George A. Calin,Carlo M. Croce +1 more
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Journal ArticleDOI
A microRNA expression signature of human solid tumors defines cancer gene targets
Stefano Volinia,George A. Calin,Chang Gong Liu,Stefan Ambs,Amelia Cimmino,Fabio Petrocca,Rosa Visone,Marilena V. Iorio,Claudia Roldo,Manuela Ferracin,Robyn L. Prueitt,Nozumu Yanaihara,Giovanni Lanza,Aldo Scarpa,Andrea Vecchione,Massimo Negrini,Curtis C. Harris,Carlo M. Croce +17 more
TL;DR: The results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes.
Journal ArticleDOI
Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia
George A. Calin,Calin Dan Dumitru,Masayoshi Shimizu,Roberta Bichi,Simona Zupo,Evan Noch,Hansjuerg Aldler,Sashi Rattan,Michael J. Keating,Kanti R. Rai,Laura Z. Rassenti,Thomas J. Kipps,Massimo Negrini,Florencia Bullrich,Carlo M. Croce +14 more
TL;DR: Detailed deletion and expression analysis shows that miR15 and miR16 are located within a 30-kb region of loss in CLL, and that both genes are deleted or down-regulated in the majority (≈68%) of CLL cases.
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MicroRNA genes are transcribed by RNA polymerase II.
TL;DR: The first direct evidence that miRNA genes are transcribed by RNA polymerase II (pol II) is presented and the detailed structure of a miRNA gene is described, for the first time, by determining the promoter and the terminator of mir‐23a∼27a‐24‐2.