miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13
| Autor: | Weijie Li, Ying Li, Shengqing Li, Lin-Tao Jia, Shengli Zhang, Shudi Xu, Shan Wang, Tao Wang, Ting Wang, Zhiwei Yang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
protein tyrosine phosphatase non-receptor type 13
0301 basic medicine Lung Neoplasms miR-26a medicine.drug_class Protein Tyrosine Phosphatase Non-Receptor Type 13 Mice Nude Antineoplastic Agents Protein tyrosine phosphatase Tyrosine-kinase inhibitor Mice 03 medical and health sciences tyrosine kinase inhibitor 0302 clinical medicine Gefitinib Carcinoma Non-Small-Cell Lung medicine Animals Humans Epidermal growth factor receptor Lung cancer Protein Kinase Inhibitors non-small cell lung cancer Mice Inbred BALB C biology business.industry medicine.disease Xenograft Model Antitumor Assays humanities respiratory tract diseases Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology PTPN13 Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Immunology Quinazolines Cancer research biology.protein epidermal growth factor receptor business Tyrosine kinase Research Paper medicine.drug Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Shudi Xu 1, 2, * , Tao Wang 3, * , Zhiwei Yang 4, * , Ying Li 1, 5, * , Weijie Li 1, 6 , Ting Wang 7 , Shan Wang 7 , Lintao Jia 7 , Shengli Zhang 4 , Shengqing Li 1 1 Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China 2 Department of Respiratory Medicine, 9th Hospital of Xi’an, Xi’an, China 3 Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, China 4 Department of Applied Physics, Xi’an Jiaotong University, Xi’an, China 5 Department of Respiratory Medicine, Shaanxi Provincial Second People's Hospital, Xi'an, China 6 Department of Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, China 7 Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China * These authors have contributed equally to this work Correspondence to: Shengqing Li, email: shengqingli@hotmail.com Shengli Zhang, email: zhangsl@mail.xjtu.edu.cn Keywords: epidermal growth factor receptor, tyrosine kinase inhibitor, non-small cell lung cancer, miR-26a, protein tyrosine phosphatase non-receptor type 13 Received: February 16, 2016 Accepted: May 23, 2016 Published: June 07, 2016 ABSTRACT Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have emerged as first-line drugs for non-small cell lung cancers (NSCLCs). However, the resistance to TKIs represents the key limitation for their therapeutic efficacy. We found that miR-26a was upregulated in gefitinib-refractory NSCLCs; miR-26a is downstream of EGFR signaling and directly targets and silences protein tyrosine phosphatase non-receptor type 13 (PTPN13) to maintain the activation of Src, a dephosphorylation substrate of PTPN13, thus reinforcing EGFR pathway in a regulatory circuit. miR-26a inhibition significantly improved NSCLC responses to gefitinib. These data revealed a novel mechanism of NSCLC resistance to TKI treatment. |
| Databáze: | OpenAIRE |
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