title: MicroRNAs associated with tumour migration, invasion and angiogenic properties in A549 and SK-Lu1 human lung adenocarcinoma cells.
abstract: OBJECTIVE
  Dysregulation in miRNA expression contributes towards the initiation and progression of metastasis by regulating multiple target genes. In this study, variations in miRNA expression profiles were investigated between high and low invasive NSCLC cell lines followed by identification of miRNAs with targets governing NSCLC's metastatic potential.
  
  
  METHODS
  Two NSCLC sub-cell lines possessing opposing migration and invasion properties were established using serial transwell invasion assays. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation. Target prediction and pathway enrichment analyses were conducted on dysregulated miRNAs using DIANA-mirPath, DIANA-microT 4.0 and TargetScan 5.2 softwares. Metastatic effects of dysregulated miRNAs were evaluated using wound healing assay, invasion assay and HUVEC angiogenesis assay following transfection with mimics and inhibitors.
  
  
  RESULTS
  A total of eleven differentially expressed miRNAs were revealed from microarray analyses, with four miRNAs validated through RT-qPCR. Three of these miRNAs were further selected for biological function validations, with only two modulating metastasis. A pathway model describing interactions between miRNAs and metastasis highlighted four major pathways: non-canonical Wnt/PCP, TGF-β, MAPK and integrin-FAK-Src signalling cascade.
  
  
  CONCLUSIONS
  These results provide a list of potential candidate metastatic markers during the classification of NSCLCs and a platform for the development of bio-therapeutics targeting these miRNA control elements.
authors.affiliation: Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chai San
authors.initials: CS
authors.lastname: Ho
authors.affiliation: Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Seow Hui
authors.initials: SH
authors.lastname: Yap
authors.affiliation: Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Neoh Hun
authors.initials: NH
authors.lastname: Phuah
authors.affiliation: Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Lionel L A
authors.initials: LL
authors.lastname: In
authors.affiliation: Institute of Biological Sciences, Division of Genetics and Molecular Biology, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Research in Biotechnology for Agriculture (CEBAR), University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: hasima@um.edu.my.
authors.forename: Noor
authors.initials: N
authors.lastname: Hasima
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003198:Computer Simulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D015398:Signal Transduction; D012984:Software; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D016023:Integrins; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Angiogenesis; Invasion; Metastasis; MicroRNA; Migration; Non-small cell lung cancer