Research Papers:

miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13

Shudi Xu, Tao Wang, Zhiwei Yang, Ying Li, Weijie Li, Ting Wang, Shan Wang, Lintao Jia, Shengli Zhang and Shengqing Li _

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Oncotarget. 2016; 7:45687-45701. https://doi.org/10.18632/oncotarget.9920

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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

Correspondence to:

Shengqing Li, email: [email protected]

Shengli Zhang, email: [email protected]

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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