Imperial College London
Alternate

ProfessorLucaMagnani

Faculty of Medicine, Department of Surgery & Cancer

Honorary Principal Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ottaviani:2018:10.1038/s41467-018-03962-x,
author = {Ottaviani, S and Stebbing, J and Frampton, AE and Zagorac, S and Krell, J and de, Giorgio A and Trabulo, SM and Nguyen, VTM and Magnani, L and Feng, H and Giovannetti, E and Funel, N and Gress, TM and Jiao, LR and Lombardo, Y and Lemoine, NR and Heeschen, C and Castellano, L},
doi = {10.1038/s41467-018-03962-x},
journal = {Nature Communications},
title = {TGF-beta induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression},
url = {http://dx.doi.org/10.1038/s41467-018-03962-x},
volume = {9},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Ottaviani,S
AU  - Stebbing,J
AU  - Frampton,AE
AU  - Zagorac,S
AU  - Krell,J
AU  - de,Giorgio A
AU  - Trabulo,SM
AU  - Nguyen,VTM
AU  - Magnani,L
AU  - Feng,H
AU  - Giovannetti,E
AU  - Funel,N
AU  - Gress,TM
AU  - Jiao,LR
AU  - Lombardo,Y
AU  - Lemoine,NR
AU  - Heeschen,C
AU  - Castellano,L
DO  - 10.1038/s41467-018-03962-x
PY  - 2018///
SN  - 2041-1723
TI  - TGF-beta induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-018-03962-x
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000431771400003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/57718
VL  - 9
ER  -
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