Title |
RETRACTED ARTICLE: EGFR and MET receptor tyrosine kinase–altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
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Published in |
Nature Medicine, December 2011
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DOI | 10.1038/nm.2577 |
Pubmed ID | |
Authors |
Michela Garofalo, Giulia Romano, Gianpiero Di Leva, Gerard Nuovo, Young-Jun Jeon, Apollinaire Ngankeu, Jin Sun, Francesca Lovat, Hansjuerg Alder, Gerolama Condorelli, Jeffrey A Engelman, Mayumi Ono, Jin Kyung Rho, Luciano Cascione, Stefano Volinia, Kenneth P Nephew, Carlo M Croce |
Abstract |
The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand their role in TKI-resistant NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors. Here we report that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only by MET. We showed that these miRNAs have important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM), apoptotic peptidase activating factor 1 (APAF-1), protein kinase C ɛ (PKC-ɛ) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 33% |
Japan | 1 | 17% |
Italy | 1 | 17% |
Unknown | 2 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Scientists | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 3 | 1% |
United Kingdom | 3 | 1% |
United States | 3 | 1% |
Spain | 2 | <1% |
Italy | 1 | <1% |
Australia | 1 | <1% |
Canada | 1 | <1% |
Mexico | 1 | <1% |
Belgium | 1 | <1% |
Other | 5 | 2% |
Unknown | 211 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 62 | 27% |
Student > Ph. D. Student | 56 | 24% |
Student > Master | 22 | 9% |
Student > Bachelor | 18 | 8% |
Student > Doctoral Student | 13 | 6% |
Other | 44 | 19% |
Unknown | 17 | 7% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 98 | 42% |
Medicine and Dentistry | 58 | 25% |
Biochemistry, Genetics and Molecular Biology | 38 | 16% |
Chemistry | 4 | 2% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 1% |
Other | 5 | 2% |
Unknown | 26 | 11% |