Article (Scientific journals)
Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity
Ullmann, Pit; Nurmik, Martin; Schmitz, Martine et al.
2019In Cancer Letters, 450, p. 32-41
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Keywords :
Colon cancer stem cell; Hypoxia; microRNA; miR-215; LGR5
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ullmann, Pit ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Nurmik, Martin ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Schmitz, Martine ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Rodriguez, Fabien ;  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 ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Felten, Paul ;  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 ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Letellier, Elisabeth ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
no
Language :
English
Title :
Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity
Publication date :
May 2019
Journal title :
Cancer Letters
ISSN :
1872-7980
Publisher :
Elsevier, Limerick, Netherlands
Volume :
450
Pages :
32-41
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR3093113 - Influence Of Hypoxia On The Metabolome Of Colon Cancer Stem Cells., 2011 (01/01/2012-30/11/2015) - Komal Baig
Funders :
Fondation Cancer
Fondation du Pélican de Mie
Available on ORBilu :
since 14 October 2019

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