Reference : Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/40668
Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity
English
Ullmann, Pit mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Nurmik, Martin mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Schmitz, Martine mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Rodriguez, Fabien mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Weilerr, Jil [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit > > Molecular Disease Mechanisms]
Baig, Komal mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Felten, Paul mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Nazarov, Petr [Luxembourg Institute of Health - LIH > Oncology, Proteome and Genome Research Unit]
NICOT, Nathalie [Luxembourg Institute of Health - LIH > Oncology, Proteome and Genome Research Unit]
Zuegel, Nikolaus [Centre Hospitalier Emile Mayrisch]
Haan, Serge mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Letellier, Elisabeth mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
May-2019
Cancer Letters
Elsevier
450
32-41
Yes
0304-3835
1872-7980
Limerick
Netherlands
[en] Colon cancer stem cell ; Hypoxia ; microRNA ; miR-215 ; LGR5
[en] Cancer stem cells, also known as tumor-initiating cells (TICs), are a population of aggressive and self-renewing cells that are responsible for the initiation and progression of many cancers, including colorectal carcinoma. Intratumoral hypoxia, i.e. reduced oxygen supply following uncontrolled proliferation of cancer cells, is thought to support TIC activity by inducing specific hypoxia-responsive mechanisms that are not yet entirely understood. Using previously established and fully characterized patient-derived TIC cultures, we could observe increased sphere and colony formation under hypoxic conditions. Mechanistically, microRNA (miRNA)-profiling experiments allowed us to identify miR-215 as one of the main hypoxia-induced miRNAs in primary colon TICs. Through stable overexpression of miR-215, followed by a set of functional in vitro and in vivo investigations, miR-215 was pinpointed as a negative feedback regulator, working against the TIC-promoting effects of hypoxia. Furthermore, we could single out LGR5, a bona fide marker of non-neoplastic intestinal stem cells, as a downstream target of hypoxia/miR-215 signaling. The strong tumor- and TIC-suppressor potential of miR-215 and the regulatory role of the hypoxia/miR-215/LGR5 axis may thus represent interesting points of attack for the development of innovative anti-CSC therapy approaches.
Fondation Cancer ; Fondation du PĂ©lican de Mie
Researchers ; Professionals
http://hdl.handle.net/10993/40668
10.1016/j.canlet.2019.02.030
FnR ; FNR3093113 > Komal Baig > > Influence of hypoxia on the metabolome of colon cancer stem cells. > 01/01/2012 > 30/11/2015 > 2011

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