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/L...Continue Reading
Citations
Jun 5, 2019·Cells·Pit UllmannElisabeth Letellier
Jul 30, 2019·Mediators of Inflammation·Zhenyu ZhouShu Qin
Nov 5, 2019·Frontiers in Cell and Developmental Biology·Mohamed A NasrNagwa El-Badri
Nov 30, 2019·Autophagy·Komal Qureshi-BaigElisabeth Letellier
Jan 24, 2020·Journal of Clinical Medicine·Hyo Jung ChoJae Youn Cheong
Dec 22, 2019·Cells·Xueqiao JiaoLixia Xiong
May 3, 2020·Journal of Experimental & Clinical Cancer Research : CR·Somshuvra BhattacharyaPilar de la Puente
Apr 21, 2020·Journal of Oncology·Xiaocheng CaoJianguo Cao
Oct 15, 2019·Technology in Cancer Research & Treatment·Xiaowei TangZhendong Cheng
Oct 2, 2020·Oncogenesis·Baoyu ChenYong Xu
Jul 3, 2020·International Journal of Molecular Sciences·Paulína PidíkovaIveta Herichova
Nov 24, 2020·Stem Cell Reviews and Reports·Alaleh RezalotfiNima Rezaei
Dec 2, 2020·Cancers·Tana MachackovaOndrej Slaby
Jan 13, 2021·Stem Cell Reviews and Reports·Lu Liu, Jürgen Borlak
Oct 31, 2020·BioMed Research International·Dan RaoShigang Duan
Feb 11, 2021·International Journal of Molecular Sciences·Andrea AngiusMaria Rosaria De Miglio
Mar 7, 2021·International Journal of Molecular Sciences·Maria Magdalena BarrecaAlice Conigliaro
Jun 28, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Yuan ChengXuelei Ma
Aug 14, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaoyu SunMinjie Wei
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Soudeh Ghafouri-FardGuive Sharifi
Oct 13, 2021·Molecular Biology Reports·Mateus de Almeida RainhoAlessandra Alves Thole
Jul 30, 2021·Recent Patents on Anti-cancer Drug Discovery·Suman Kumar Ray, Sukhes Mukherjee