miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13
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Shudi Xu1,2,*, Tao Wang3,*, Zhiwei Yang4,*, Ying Li1,5,*, Weijie Li1,6, Ting Wang7, Shan Wang7, Lintao Jia7, Shengli Zhang4, Shengqing Li1
1Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
2Department of Respiratory Medicine, 9th Hospital of Xi’an, Xi’an, China
3Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, China
4Department of Applied Physics, Xi’an Jiaotong University, Xi’an, China
5Department of Respiratory Medicine, Shaanxi Provincial Second People's Hospital, Xi'an, China
6Department of Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, China
7Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China
*These authors have contributed equally to this work
Shengqing Li, email: email@example.com
Shengli Zhang, email: firstname.lastname@example.org
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
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.
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