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http://dx.doi.org/10.7314/APJCP.2012.13.1.255

MicroRNA-214 Regulates the Acquired Resistance to Gefitinib via the PTEN/AKT Pathway in EGFR-mutant Cell Lines  

Wang, Yong-Sheng (Department of Oncology, Shanghai Pulmonary Hospital, Tongji University)
Wang, Yin-Hua (Department of Oncology, The Second People's Hospital of Wuhu City, Wannan Medical College)
Xia, Hong-Ping (Department of Chemistry, University of Hong Kong)
Zhou, Song-Wen (Department of Oncology, Shanghai Pulmonary Hospital, Tongji University)
Schmid-Bindert, Gerald (Department of Interdisciplinary Thoracic Oncology, University Medical Center Mannheim, Heidelberg University)
Zhou, Cai-Cun (Department of Oncology, Shanghai Pulmonary Hospital, Tongji University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.1, 2012 , pp. 255-260 More about this Journal
Abstract
Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.
Keywords
MiR-214; acquired resistance; gefitinib; PTEN; signaling pathway;
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