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Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity.

Abstract：

: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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Ullmann P,Nurmik M,Schmitz M,Rodriguez F,Weiler J,Qureshi-Baig K,Felten P,Nazarov PV,Nicot N,Zuegel N,Haan S,Letellier E

doi

10.1016/j.canlet.2019.02.030

subject

Has Abstract

pub_date

2019-05-28 00:00:00

pages

32-41

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(19)30108-9

journal_volume

450

pub_type

杂志文章

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