An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation

التفاصيل البيبلوغرافية
العنوان: An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation
المؤلفون: Sarit Tabak, Mariana Brait, David Sidransky, Takenori Ogawa, Wayne M. Koch, Evgeny Izumchenko, Shahnaz Begum, Mohammad O. Hoque, Steven A. Ahrendt, Masamichi Hayashi, Fayez J. Jabboure, William H. Westra
المصدر: Scientific Reports
بيانات النشر: Nature Publishing Group, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Male, Lung Neoplasms, medicine.medical_treatment, Cell, Gene Dosage, Biology, Allelic Imbalance, Bioinformatics, Gene dosage, Article, Targeted therapy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, microRNA, medicine, Humans, Genetic Predisposition to Disease, Lung cancer, Genetic Association Studies, 030304 developmental biology, Neoplasm Staging, 0303 health sciences, Multidisciplinary, Cell growth, Genome, Human, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Reproducibility of Results, Middle Aged, medicine.disease, 3. Good health, Gene expression profiling, Gene Expression Regulation, Neoplastic, MicroRNAs, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Cancer research, Female
الوصف: 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.
اللغة: English
تدمد: 2045-2322
DOI: 10.1038/srep13236
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe6aa00ff38a8ae2f985576621be9b11Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....fe6aa00ff38a8ae2f985576621be9b11
قاعدة البيانات: OpenAIRE
الوصف
تدمد:20452322
DOI:10.1038/srep13236