TY - JOUR
T1 - An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer
T2 - Clinical significance of MIR-23b-3p deregulation
AU - Begum, Shahnaz
AU - Hayashi, Masamichi
AU - Ogawa, Takenori
AU - Jabboure, Fayez J.
AU - Brait, Mariana
AU - Izumchenko, Evgeny
AU - Tabak, Sarit
AU - Ahrendt, Steven A.
AU - Westra, William H.
AU - Koch, Wayne
AU - Sidransky, David
AU - Hoque, Mohammad O.
PY - 2015/8/28
Y1 - 2015/8/28
N2 - 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.
AB - 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.
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U2 - 10.1038/srep13236
DO - 10.1038/srep13236
M3 - Article
C2 - 26314549
AN - SCOPUS:84940496099
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 13236
ER -