title: MicroRNAs associated with increased AKT gene number in human lung carcinoma.
abstract: MicroRNA (miRNA) expression profiles were examined in 3 groups of lung carcinomas that had been stratified by increases in AKT1 or AKT2 gene number. Microarray analysis using 2000 probes revealed 87 miRNAs that were up-regulated and 32 down-regulated miRNAs in carcinomas harboring amplification or high-level polysomy of the AKT1 (AKT1+), as well as 123 up-regulated and 83 down-regulated miRNAs in those of the AKT2 genes (AKT2+), in comparison with carcinomas harboring disomy of both (AKTd/d). In total, 182 miRNAs were up-regulated in AKT1+ or AKT2+, compared with AKTd/d. Among these, 28 miRNAs were up-regulated in both the AKT1+ and AKT2+ groups, with a log2 ratio between 1.02 and 3.71 relative to AKTd/d group, including all miR-200 family members. Quantitative real-time polymerase chain reaction showed that carcinomas exhibiting lymph vessel invasion had significantly lower expression of miR-200a (P=.0230) and miR-200b (P=.0168), regardless of the status of the AKT genes. Moreover, a detailed statistical analysis revealed that, in adenocarcinoma and in the early stage of carcinomas (pathologic stage I/II), expression of miR-200a was higher in the AKT2+ group compared with the AKT1+ group, and these differences were statistically significant (P=.0334 and P=.0239, respectively). However, the expression of miR-200a was not significantly correlated with the expression of its target, the zinc finger E-box-binding homeobox 1 (ZEB1; P=.3801) or E-cadherin (P=.2840), a marker of the epithelial-mesenchymal transition. These results suggest that AKT2 can regulate miR-200a in a histology- or stage-specific manner and that this regulation is independent of subsequent involvement of miR-200a in epithelial-mesenchymal transition.
authors.affiliation: Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Akita 010-8543, Japan.
authors.forename: Akiteru
authors.initials: A
authors.lastname: Goto
authors.affiliation: Department of Pathology, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan. Electronic address: ydobashi@omiya.jichi.ac.jp.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Dobashi
authors.affiliation: Department of Thoracic Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Tsubochi
authors.affiliation: Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Akita 010-8543, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Maeda
authors.affiliation: Department of Molecular and Cellular Pathology, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Akishi
authors.initials: A
authors.lastname: Ooi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D015820:Cadherins / Q000032:analysis; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000032:analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C494918:AKT1 protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Amplification; Lung cancer; MicroRNA; ZEB1; miR-200