dc.contributor.author | Ottaviani, S | en_US |
dc.contributor.author | Stebbing, J | en_US |
dc.contributor.author | Frampton, AE | en_US |
dc.contributor.author | Zagorac, S | en_US |
dc.contributor.author | Krell, J | en_US |
dc.contributor.author | de Giorgio, A | en_US |
dc.contributor.author | Trabulo, SM | en_US |
dc.contributor.author | Nguyen, VTM | en_US |
dc.contributor.author | Magnani, L | en_US |
dc.contributor.author | Feng, H | en_US |
dc.contributor.author | Giovannetti, E | en_US |
dc.contributor.author | Funel, N | en_US |
dc.contributor.author | Gress, TM | en_US |
dc.contributor.author | Jiao, LR | en_US |
dc.contributor.author | Lombardo, Y | en_US |
dc.contributor.author | Lemoine, NR | en_US |
dc.contributor.author | Heeschen, C | en_US |
dc.contributor.author | Castellano, L | en_US |
dc.date.accessioned | 2018-06-05T15:01:11Z | |
dc.date.available | 2018-03-26 | en_US |
dc.date.issued | 2018-05-10 | en_US |
dc.date.submitted | 2018-05-24T13:39:45.439Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/39324 | |
dc.description.abstract | TGF-β/Activin induces epithelial-to-mesenchymal transition and stemness in pancreatic ductal adenocarcinoma (PDAC). However, the microRNAs (miRNAs) regulated during this response have remained yet undetermined. Here, we show that TGF-β transcriptionally induces MIR100HG lncRNA, containing miR-100, miR-125b and let-7a in its intron, via SMAD2/3. Interestingly, we find that although the pro-tumourigenic miR-100 and miR-125b accordingly increase, the amount of anti-tumourigenic let-7a is unchanged, as TGF-β also induces LIN28B inhibiting its maturation. Notably, we demonstrate that inactivation of miR-125b or miR-100 affects the TGF-β-mediated response indicating that these miRNAs are important TGF-β effectors. We integrate AGO2-RIP-seq with RNA-seq to identify the global regulation exerted by these miRNAs in PDAC cells. Transcripts targeted by miR-125b and miR-100 significantly overlap and mainly inhibit p53 and cell-cell junctions' pathways. Together, we uncover that TGF-β induces an lncRNA, whose encoded miRNAs, miR-100, let-7a and miR-125b play opposing roles in controlling PDAC tumourigenesis. | en_US |
dc.description.sponsorship | Dutch Cancer Society, KWF#10401 grant to E.G., Italian Association for Cancer Research AIRC/Start-Up grant to E.G., Istituto Toscano Tumouri ITT-grant to N.F. and E.G., and the Regione Toscana “Progetto DIAMANTE”/FAS grant to N.F. and E.G. The authors thank Prof. Matthias Löhr and Dr Rainer Heuchel at Karolinska University Hospital, Stockholm, Sweden, for providing the TGF-β1 and empty vector expressing PANC-1 cells. This work used the computing resources of the UK MEDical BIOinformatics partnership—aggregation, integration, visualization, and analysis of large, complex data (UK MED-BIO) which is supported by the Medical Research Council [grant number MR/L01632X/1]. | en_US |
dc.format.extent | 1845 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0 | |
dc.subject | Animals | en_US |
dc.subject | Carcinogenesis | en_US |
dc.subject | Carcinoma, Pancreatic Ductal | en_US |
dc.subject | Cell Line, Tumor | en_US |
dc.subject | Datasets as Topic | en_US |
dc.subject | Disease Progression | en_US |
dc.subject | Female | en_US |
dc.subject | Gene Expression Regulation, Neoplastic | en_US |
dc.subject | Humans | en_US |
dc.subject | Introns | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Nude | en_US |
dc.subject | MicroRNAs | en_US |
dc.subject | Pancreas | en_US |
dc.subject | Pancreatic Neoplasms | en_US |
dc.subject | RNA, Small Interfering | en_US |
dc.subject | RNA-Binding Proteins | en_US |
dc.subject | Signal Transduction | en_US |
dc.subject | Transforming Growth Factor beta1 | en_US |
dc.subject | Up-Regulation | en_US |
dc.subject | Xenograft Model Antitumor Assays | en_US |
dc.title | TGF-β induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s) 2018. | |
dc.identifier.doi | 10.1038/s41467-018-03962-x | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29748571 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 9 | en_US |
dcterms.dateAccepted | 2018-03-26 | en_US |