title: Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells.
abstract: MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor-kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Seong-Lan
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Lee
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Hyun Ahm
authors.initials: HA
authors.lastname: Sohn
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, 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: Hyo Sung
authors.initials: HS
authors.lastname: Jeon
authors.affiliation: Department of Cell Biology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Joon H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Chang Gyo
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Genome Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
authors.affiliation: Department of Thoracic Surgery, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Yoo Sang
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Jaeku
authors.initials: J
authors.lastname: Kang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation
chemical_list: D018398:Homeodomain Proteins; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C097899:homeobox protein HOXA9
keywords: EMT; HOXA9; NF-κB; NSCLC; miR-196b