miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13.
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.
Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.|Department of Respiratory Medicine, 9th Hospital of Xi'an, Xi'an, China.
Shudi
S
Xu
Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, China.
Tao
T
Wang
Department of Applied Physics, Xi'an Jiaotong University, Xi'an, China.
Zhiwei
Z
Yang
Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.|Department of Respiratory Medicine, Shaanxi Provincial Second People's Hospital, Xi'an, China.
Ying
Y
Li
Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.|Department of Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, China.
Weijie
W
Li
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Ting
T
Wang
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Shan
S
Wang
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Lintao
L
Jia
Department of Applied Physics, Xi'an Jiaotong University, Xi'an, China.
Shengli
S
Zhang
Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Shengqing
S
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000096:biosynthesis* / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D000077156:Gefitinib; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D011799:Quinazolines; C528163:MIRN26 microRNA, human; C516742:PTPN13 protein, human
epidermal growth factor receptor; miR-26a; non-small cell lung cancer; protein tyrosine phosphatase non-receptor type 13; tyrosine kinase inhibitor