2026-06-14T03:31:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/64492024-11-29T22:22:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2018-05-10 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. 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 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