TY - JOUR AB - During cancer progression, some tumor cells show changes in their plasticity by morphological and phenotypical conversions, as an expression of mesenchymal markers and loss of epithelial markers, collectively referred to as epithelial-mesenchymal transition (EMT). EMT has been increasingly recognized as a critical phenomenon in lung cancer progression. The goal of this study was to identify microRNAs involved in lung cancer progression. A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in mesenchymal-like lung cancer cells. The role of miR‑146a in lung cancer progression was measured by invasion and migration assays in vitro. Bioinformatics and luciferase report assays were used to identify the target of miR‑146a. The expression of miR‑146a was reduced in mesenchymal-like lung cancer cell lines. The overexpression of miR‑146a induced a marked reduction of the mesenchymal marker and increase the epithelial marker in lung cancer cell lines. Moreover, the overexpression of miR‑146a suppressed lung cancer cell migration and invasion. Co-treatment with miR‑146a and gefitinib treatment showed a significant reduction of invasion in the resistant lung cancer cells induced by EMT. The expression of miR‑146a was downregulated in advanced lung cancer tissues. Insulin receptor substrate 2 (IRS2), an adaptor protein that modulates normal growth, metabolism, survival, and differentiation, was identified as a target of miR‑146a. miR‑146a regulated the expression of IRS2 at the mRNA and protein levels. These data demonstrate for the first time that miR‑146a suppresses lung cancer progression by repressing IRS2 expression. This provides new insight into the post-transcriptional regulation of lung cancer progression by miRNAs, a potential approach for the treatment of lung cancer. AD - Department of Anesthesiology and Pain Medicine, Konyang University Hospital, Daejeon, Republic of Korea The Molecular Diagnostics and Imaging Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Myunggok Research Institute for Medical Science, Konyang University, Daejeon, Republic of Korea Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Clinical Drug Manufacturing Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea Department of Chemical Engineering, University of Massachusetts Lowell, MA, USA Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea Department of Thoracic Surgery, Konyang University Hospital, Daejeon, Republic of Korea Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea AU - Park,Dong,Ho AU - Jeon,Hyo ,Sung AU - Lee,Soo,Young AU - Choi,Yi ,Young AU - Lee,Hae ,Woo AU - Yoon,Seongkyu AU - Lee,Jae ,Chel AU - Yoon,Yoo ,Sang AU - Kim,Dae ,Sung AU - Na,Moon ,Jun AU - Kwon,Sun ,Jung AU - Kim,Dong,Sun AU - Kang,Jaeku AU - Park,Jae,Yong AU - Son,Ji ,Woong DA - 2015/10/01 DO - 10.3892/ijo.2015.3111 EP - 1553 IS - 4 JO - Int J Oncol KW - lung cancer microRNA epithelial mesenchymal transition drug resistance invasion PY - 2015 SN - 1019-6439 1791-2423 SP - 1545 ST - MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2 T2 - International Journal of Oncology TI - MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2 UR - https://doi.org/10.3892/ijo.2015.3111 VL - 47 ER -