Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family
MicroRNAs(miRNAs) are post-transcriptional regulators of gene expressioncritical for organismal viability. Changes inmiRNAactivity arecommonin cancer, buthowthese changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep...
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Cold Spring Harbor Laboratory
2017
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| Online Access: | http://hdl.handle.net/1721.1/112212 https://orcid.org/0000-0001-8353-9316 https://orcid.org/0000-0002-2902-7288 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-1465-1691 |
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| author | JnBaptiste, Courtney Kenneil Gurtan, Allan Thai, Kevin K. Lu, Victoria Bhutkar, Arjun Jacks, Tyler E. Sharp, Phillip A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology JnBaptiste, Courtney Kenneil Gurtan, Allan Thai, Kevin K. Lu, Victoria Bhutkar, Arjun Jacks, Tyler E. Sharp, Phillip A. |
| author_sort | JnBaptiste, Courtney Kenneil |
| collection | MIT |
| description | MicroRNAs(miRNAs) are post-transcriptional regulators of gene expressioncritical for organismal viability. Changes inmiRNAactivity arecommonin cancer, buthowthese changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated bymiRNAs. Wepresent analysis of the gene expression and phenotypic changes associated with globalmiRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genesImp1, Imp2, and Imp3(Imp1–3) that is up-regulated primarily transcriptionally > 100-fold uponDicer loss and is resistant to resilencing by complete restoration of miRNA activity. This Dicer-resistant epigenetic switch confers tumorigenicity to these cells. Let-7 targets Imp1–3 are required for this tumorigenicity and feed back to reinforce and sustain expression of the oncogenic network. Together, these Dicer-resistant genes constitute an mRNA expression signature that is present in numerous human cancers and is associated with poor survival. |
| first_indexed | 2024-09-23T16:57:03Z |
| format | Article |
| id | mit-1721.1/112212 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:57:03Z |
| publishDate | 2017 |
| publisher | Cold Spring Harbor Laboratory |
| record_format | dspace |
| spelling | mit-1721.1/1122122022-10-03T09:21:34Z Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family JnBaptiste, Courtney Kenneil Gurtan, Allan Thai, Kevin K. Lu, Victoria Bhutkar, Arjun Jacks, Tyler E. Sharp, Phillip A. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT JnBaptiste, Courtney Kenneil Gurtan, Allan Thai, Kevin K. Lu, Victoria Bhutkar, Arjun Jacks, Tyler E. Sharp, Phillip A. MicroRNAs(miRNAs) are post-transcriptional regulators of gene expressioncritical for organismal viability. Changes inmiRNAactivity arecommonin cancer, buthowthese changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated bymiRNAs. Wepresent analysis of the gene expression and phenotypic changes associated with globalmiRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genesImp1, Imp2, and Imp3(Imp1–3) that is up-regulated primarily transcriptionally > 100-fold uponDicer loss and is resistant to resilencing by complete restoration of miRNA activity. This Dicer-resistant epigenetic switch confers tumorigenicity to these cells. Let-7 targets Imp1–3 are required for this tumorigenicity and feed back to reinforce and sustain expression of the oncogenic network. Together, these Dicer-resistant genes constitute an mRNA expression signature that is present in numerous human cancers and is associated with poor survival. United States. Public Health Service (Grant R01CA133404) National Cancer Institute (U.S.) (Grant P01CA42063) Marie D. and Pierre Casimir-Lambert 2017-11-16T21:22:45Z 2017-11-16T21:22:45Z 2017-04 2017-03 2017-10-27T19:52:48Z Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 http://hdl.handle.net/1721.1/112212 JnBaptiste et al. “Dicer Loss and Recovery Induce an Oncogenic Switch Driven by Transcriptional Activation of the Oncofetal Imp1–3 Family.” Genes & Development 31, 7 (April 2017): 674–687 © 2017 JnBaptiste et al https://orcid.org/0000-0001-8353-9316 https://orcid.org/0000-0002-2902-7288 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-1465-1691 http://dx.doi.org/10.1101/GAD.296301.117 Genes & Development Creative Commons Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory Press |
| spellingShingle | JnBaptiste, Courtney Kenneil Gurtan, Allan Thai, Kevin K. Lu, Victoria Bhutkar, Arjun Jacks, Tyler E. Sharp, Phillip A. Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family |
| title | Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family |
| title_full | Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family |
| title_fullStr | Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family |
| title_full_unstemmed | Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family |
| title_short | Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1–3 family |
| title_sort | dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal imp1 3 family |
| url | http://hdl.handle.net/1721.1/112212 https://orcid.org/0000-0001-8353-9316 https://orcid.org/0000-0002-2902-7288 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-1465-1691 |
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