Open AccessTargeting the Wnt‐Regulatory Protein CTNNBIP1 by microRNA‐214 Enhances the Stemness and Self‐Renewal of Cancer Stem‐Like Cells in Lung Adenocarcinomas
Author(s) -
Qi Wei,
Chen Junying,
Cheng Xiaoming,
Huang Jiani,
Xiang Tong,
Li Qijing,
Long Haixia,
Zhu Bo
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2188
Subject(s) - biology , microrna , homeobox protein nanog , wnt signaling pathway , cancer stem cell , stem cell , cancer research , downregulation and upregulation , microbiology and biotechnology , cancer , signal transduction , genetics , gene , embryonic stem cell , induced pluripotent stem cell
A bstract A novel hypothesis in cancer biology proposes that cancer growth is driven by cancer stem‐like cells (CSLCs), also called tumor‐initiating cells, which can self‐renew and differentiate into multilineage progeny in a fashion similar to stem cells. However, the impact and underlying mechanisms of this process in lung adenocarcinoma (LAC) remain to be elucidated. Here, we report that microRNA‐214 (miR‐214) contributes to cell self‐renewal by directly targeting catenin beta interacting protein 1 (CTNNBIP1), a member of the Wnt signaling pathway. We demonstrate that miR‐214 overexpression enhances stem‐like properties in LAC cells and that miR‐214 shows increased expression in CSLCs derived from primary tumor tissue and from two LAC cell lines (A549 and NCI‐H1650). Strikingly, downregulation of miR‐214 expression in CSLCs resulted in a significant decrease in spheroid formation and the expression of the stem‐cell markers Nanog, Oct‐4, and Sox‐2. Finally, CTNNBIP1 was identified as a target of miR‐214. miR‐214 expression in LAC was negatively correlated with CTNNBIP1 expression and positively correlated with differentiated cellular states. Moreover, CTNNBIP1 expression correlated with longer overall survival in LAC patients. This study reveals that miR‐214 plays a critical role in CSLC self‐renewal and stemness by targeting CTNNBIP1. The identification of this functional miR‐214‐CTNNBIP1 interaction that regulates self‐renewal in CSLCs has the potential to direct the development of novel therapeutic strategies for LAC. S tem C ells 2015;33:3423–3436