title: An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation.
abstract: In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes. We also tested a subset of matched samples by microRNA expression array, and integrated them to identify microRNAs positioned in allelic imbalance area. Our findings support that most of the identified deregulated microRNAs (miR-21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression of miR-23b was revealed to be a significantly poor prognostic factor of recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32-4.29) and overall survival (HR = 2.35, P = 0.005, 95%CI: 1.30-4.19) in multivariable analysis. In addition, overexpression of miR-23b in H1838 cell line significantly increased cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines significantly decreased cell doubling time. In summary, integration of genomic analysis and microRNA expression profiling could identify novel cancer-related microRNAs, and miR-23b could be a potential prognostic marker for early stage NSCLCs. Further biological studies of miR-23b are warranted for the potential development of targeted therapy.
authors: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Shahnaz
authors: S
authors: Begum
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Masamichi
authors: M
authors: Hayashi
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Takenori
authors: T
authors: Ogawa
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Fayez J
authors: FJ
authors: Jabboure
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Mariana
authors: M
authors: Brait
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Evgeny
authors: E
authors: Izumchenko
authors: Rosetta Genomics Ltd. 10 Plaut St., Rehovot, Israel, 76706.
authors: Sarit
authors: S
authors: Tabak
authors: Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213 USA.
authors: Steven A
authors: SA
authors: Ahrendt
authors: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: William H
authors: WH
authors: Westra
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Wayne
authors: W
authors: Koch
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: David
authors: D
authors: Sidransky
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.|Department of Urology, Johns Hopkins University, Baltimore, Maryland, 21231 USA.|Department of Oncology, Johns Hopkins University, Baltimore, Maryland, 21231 USA.
authors: Mohammad O
authors: MO
authors: Hoque
mesh_terms: D022981:Allelic Imbalance; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs