{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T13:36:56Z","timestamp":1770644216788,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81360004"],"award-info":[{"award-number":["81360004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2018,4]]},"abstract":"Abstract<\/jats:title>Epidermal growth receptor (EGFR<\/jats:styled-content>)\u2010targeted tyrosine kinase inhibitors (TKI<\/jats:styled-content>s) have emerged as first\u2010line drugs for advanced non\u2010small\u2010cell lung cancer (NSCLC<\/jats:styled-content>) patients with EFGR<\/jats:styled-content> mutations. However, most patients with NSCLC<\/jats:styled-content> show acquired resistance to EGFR<\/jats:styled-content>\u2010TKI<\/jats:styled-content>s, and low expression of NF<\/jats:styled-content>1 is a mechanism of EGFR<\/jats:styled-content>\u2010TKI<\/jats:styled-content> resistance in lung cancer. However, the mechanism by which NF<\/jats:styled-content>1 is downregulated in EGFR<\/jats:styled-content>\u2010TKI<\/jats:styled-content>\u2010resistant NSCLC<\/jats:styled-content> is unclear. Here, we found the increased expression of miR\u2010641 in NSCLC<\/jats:styled-content> cells and human NSCLC<\/jats:styled-content> samples with resistance to TKI<\/jats:styled-content> compared to those with sensitive to TKI<\/jats:styled-content>. In addition, our in vitro<\/jats:italic> experiments show that overexpression of miR\u2010641 induces TKI<\/jats:styled-content> resistance in NSCLC<\/jats:styled-content> cells. Furthermore, we identified that miR\u2010641 activates ERK<\/jats:styled-content> signaling by direct targeting of neurofibromatosis 1 (NF<\/jats:styled-content>1) in NSCLC<\/jats:styled-content> cells. Our data show that overexpression of NF<\/jats:styled-content>1 or silencing of ERK<\/jats:styled-content> can block miR\u2010641\u2010induced resistance of NSCLC<\/jats:styled-content> cells to erlotinib treatment. Importantly, our animal experiments show that combination of miR\u2010641 inhibition and erlotinib treatment can significantly inhibit erlotinib\u2010resistant NSCLC<\/jats:styled-content> growth, inhibit proliferation and induce apoptosis compared to single\u2010drug treatment. Our findings suggest that increased expression of miR\u2010641 significantly contributes to erlotinib resistance development in NSCLC<\/jats:styled-content> cells through activating ERK<\/jats:styled-content> signaling by targeting NF<\/jats:styled-content>1 and that inhibition of miR\u2010641 may reverse acquired resistance of NSCLC<\/jats:styled-content> cells to erlotinib treatment.<\/jats:p>","DOI":"10.1002\/cam4.1326","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T10:02:43Z","timestamp":1519898563000},"page":"1394-1403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Increased expression of miR\u2010641 contributes to erlotinib resistance in non\u2010small\u2010cell lung cancer cells by targeting NF<\/scp>1"],"prefix":"10.1002","volume":"7","author":[{"given":"Juan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The General Hospital of Ningxia Medical University Yinchuan 750004 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie\u2010da","family":"Cui","sequence":"additional","affiliation":[{"name":"Ningxia Medical University Yinchuan 750004 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010tong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The General Hospital of Ningxia Medical University Yinchuan 750004 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine The General Hospital of Ningxia Medical University Yinchuan 750004 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-6070","authenticated-orcid":false,"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Cancer Center Daping Hospital and Research Institute of Surgery Third Military Medical University Chongqing 400042 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0741"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62101-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2580"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00246-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2947"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2017.1355243"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.lungcan.2013.11.003","article-title":"MiR\u201021 overexpression is associated with acquired resistance of EGFR\u2010TKI in non\u2010small cell lung cancer","volume":"83","author":"Jie Z.","year":"2014","journal-title":"Lung Cancer"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/s41598-017-00901-6","article-title":"Down\u2010regulation of miR\u2010214 reverses erlotinib resistance in non\u2010small\u2010cell lung cancer through up\u2010regulating LHX6 expression","volume":"7","author":"Liao J.","year":"2017","journal-title":"Sci. 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