2026-06-14T10:38:46Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/64492024-11-29T22:22:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Ottaviani, Silvia
author
Stebbing, Justin
author
Frampton, Adam E
author
Zagorac, Sladjana
author
Krell, Jonathan
author
de Giorgio, Alexander
author
Trabulo, Sara M
author
Nguyen, Van T M
author
Magnani, Luca
author
Feng, Hugang
author
Giovannetti, Elisa
author
Funel, Niccola
author
Gress, Thomas M
author
Jiao, Long R
author
Lombardo, Ylenia
author
Lemoine, Nicholas R
author
Heeschen, Christopher
author
Castellano, Leandro
funder
Action Against Cancer
funder
Pancreatic Cancer UK
funder
Academy of Medical Sciences (Reino Unido)
funder
Royal College of Surgeons of Edinburgh
funder
Colin McDavid Family Trust
funder
No Surrender Cancer Trust
funder
Ralph Bates Pancreatic Cancer Research Fund
funder
Dutch Cancer Society (Holanda)
funder
Italian Association for Cancer Research
funder
Tumour Institute of Tuscany (Italia)
funder
Regione Toscana "Progetto DIAMANTE"/FAS grant
funder
Medical Research Council (Reino Unido)
2018-09-24T11:15:11Z
2018-09-24T11:15:11Z
2018-05-10
Nat Commun. 2018; 9(1): 1845.
10.1038/s41467-018-03962-x
2041-1723
2041-1723
Nature communications
29748571
http://hdl.handle.net/20.500.12105/6449
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.
eng
CANCER STEM-CELLS
PANCREATIC TUMOR-GROWTH
MESENCHYMAL TRANSITION
LASER MICRODISSECTION
SELF-RENEWAL
EXPRESSION
MICRORNAS
TARGET
ADENOCARCINOMA
BIOGENESIS
TGF-β induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression
journal article
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