Title |
Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma
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Published in |
Molecular Cancer, June 2017
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DOI | 10.1186/s12943-017-0669-9 |
Pubmed ID | |
Authors |
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li |
Abstract |
The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness. The oncogenic effects of microRNA-455-3p (miR-455-3p) on ESCC chemoresistance and tumorigenesis were examined by in vivo and in vitro chemoresistance, tumorsphere formation, side-population, and in vivo limiting dilution assays. The roles of miR-455-3p in activation of the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad pathways were determined by luciferase and RNA immunoprecipitation assays. We found that miR-455-3p played essential roles in ESCC chemoresistance and tumorigenesis. Treatment with a miR-455-3p antagomir dramatically chemosensitized ESCC cells and reduced the subpopulations of CD90(+) and CD271(+) T-ICs via deactivation of multiple stemness-associated pathways, including Wnt/β-catenin and TGF-β signaling. Importantly, miR-455-3p exhibited aberrant upregulation in various human cancer types, and was significantly associated with decreased overall survival of cancer patients. Our results demonstrate that miR-455-3p functions as an oncomiR in ESCC progression and may provide a potential therapeutic target to achieve better clinical outcomes in cancer patients. |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 19 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 4 | 21% |
Researcher | 4 | 21% |
Student > Ph. D. Student | 1 | 5% |
Other | 1 | 5% |
Professor > Associate Professor | 1 | 5% |
Other | 0 | 0% |
Unknown | 8 | 42% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 5 | 26% |
Psychology | 2 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Agricultural and Biological Sciences | 1 | 5% |
Social Sciences | 1 | 5% |
Other | 1 | 5% |
Unknown | 8 | 42% |