title: Targeting the Wnt-Regulatory Protein CTNNBIP1 by microRNA-214 Enhances the Stemness and Self-Renewal of Cancer Stem-Like Cells in Lung Adenocarcinomas.
abstract: 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.
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Wei
authors: W
authors: Qi
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Junying
authors: J
authors: Chen
authors: Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Xiaoming
authors: X
authors: Cheng
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Jiani
authors: J
authors: Huang
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Tong
authors: T
authors: Xiang
authors: Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
authors: Qijing
authors: Q
authors: Li
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors: Haixia
authors: H
authors: Long
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.|Biomedical Analysis Center, Third Military Medical University, Chongqing, People's Republic of China.
authors: Bo
authors: B
authors: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C411982:CTNNBIP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm
keywords: Cancer stem-like cells; Lung adenocarcinoma; MicroRNAs; Self-renewal; Wnt signaling pathway