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.
N1 - Funding Information:
We thank Dr. Prodipto Pal, for helping us in bioinformatic analysis of SNP array data. Grant Support: S. Begum is supported by a Young Clinical Scientist Award(YCSA) from the Flight Attendant Medical Research Institute (FAMRI, Miami, FL, USA), and M.O. Hoque is supported by the Young Investigator Award from the International Association for the Study of Lung Cancer and Clinical Innovative Award from FAMRI (Miami, FL, USA). This work was also supported by National Cancer Institute grant U01-CA84986.
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 -
