title: MicroRNA-146a inhibits epithelial mesenchymal transition in non-small cell lung cancer by targeting insulin receptor substrate 2.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Park
authors.affiliation: The Molecular Diagnostics and Imaging Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyo Sung
authors.initials: HS
authors.lastname: Jeon
authors.affiliation: Myunggok Research Institute for Medical Science, Konyang University, Daejeon, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Clinical Drug Manufacturing Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.
authors.forename: Hae Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Chemical Engineering, University of Massachusetts Lowell, MA, USA.
authors.forename: Seongkyu
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Chel
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Thoracic Surgery, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Yoo Sang
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Moon Jun
authors.initials: MJ
authors.lastname: Na
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Jaeku
authors.initials: J
authors.lastname: Kang
authors.affiliation: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering