Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma
Abstract Background 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12943-017-0669-9 |
| _version_ | 1817985990420070400 |
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| author | Aibin Liu Jinrong Zhu Geyan Wu Lixue Cao Zhanyao Tan Shuxia Zhang Lili Jiang Jueheng Wu Mengfeng Li Libing Song Jun Li |
| author_facet | Aibin Liu Jinrong Zhu Geyan Wu Lixue Cao Zhanyao Tan Shuxia Zhang Lili Jiang Jueheng Wu Mengfeng Li Libing Song Jun Li |
| author_sort | Aibin Liu |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-04-14T00:04:42Z |
| format | Article |
| id | doaj.art-453c7ce46eab4e77956f74103b90892b |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-14T00:04:42Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-453c7ce46eab4e77956f74103b90892b2022-12-22T02:23:34ZengBMCMolecular Cancer1476-45982017-06-0116111210.1186/s12943-017-0669-9Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinomaAibin Liu0Jinrong Zhu1Geyan Wu2Lixue Cao3Zhanyao Tan4Shuxia Zhang5Lili Jiang6Jueheng Wu7Mengfeng Li8Libing Song9Jun Li10Program of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityProgram of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityProgram of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityProgram of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityProgram of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityProgram of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityKey Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical UniversityDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-sen UniversityState Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen UniversityProgram of Cancer Research, Affiliated Guangzhou Women and Children’s Hospital, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12943-017-0669-9miR-455-3pChemoresistanceEsophageal squamous cell carcinomaOncomiR |
| spellingShingle | Aibin Liu Jinrong Zhu Geyan Wu Lixue Cao Zhanyao Tan Shuxia Zhang Lili Jiang Jueheng Wu Mengfeng Li Libing Song Jun Li Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma Molecular Cancer miR-455-3p Chemoresistance Esophageal squamous cell carcinoma OncomiR |
| title | Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma |
| title_full | Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma |
| title_fullStr | Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma |
| title_full_unstemmed | Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma |
| title_short | Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma |
| title_sort | antagonizing mir 455 3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma |
| topic | miR-455-3p Chemoresistance Esophageal squamous cell carcinoma OncomiR |
| url | http://link.springer.com/article/10.1186/s12943-017-0669-9 |
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