TY - JOUR
T1 - A Functional Genomic Approach Identifies FAL1 as an Oncogenic Long Noncoding RNA that Associates with BMI1 and Represses p21 Expression in Cancer
AU - Hu, Xiaowen
AU - Feng, Yi
AU - Zhang, Dongmei
AU - Zhao, Sihai D.
AU - Hu, Zhongyi
AU - Greshock, Joel
AU - Zhang, Youyou
AU - Yang, Lu
AU - Zhong, Xiaomin
AU - Wang, Li Ping
AU - Jean, Stephanie
AU - Li, Chunsheng
AU - Huang, Qihong
AU - Katsaros, Dionyssios
AU - Montone, Kathleen T.
AU - Tanyi, Janos L.
AU - Lu, Yiling
AU - Boyd, Jeff
AU - Nathanson, Katherine L.
AU - Li, Hongzhe
AU - Mills, Gordon B.
AU - Zhang, Lin
N1 - Funding Information:
We thank the Tumorscape team and Dr. Nelly Auersperg for providing SNP arrays and HOSE cells, respectively. This work was supported, in whole or in part, by the Basser Research Center for BRCA (K.L.N. and L.Z.), the NIH (grant R01CA142776 to L.Z., grant P50CA083638 to J.B. and L.Z., grant P50CA083639 to G.B.M., grant P50CA098258 to G.B.M., grant U24CA143883 to G.B.M., grant P01CA099031 to G.B.M., grant R01CA127334 to H.L., grant R01CA148759 to Q.H., and grant K12HD000849 to J.L.T.), the Ovarian Cancer Research Fund (L.Z. and X.H.), the Breast Cancer Alliance (L.Z.), Department of Defense (L.Z.), and the Marsha Rivkin Center for Ovarian Cancer Research (L.Z.). D.Z. and L.Y were supported by the China Scholarship Council. Functional Proteomics RPPA Core at the MD Anderson Cancer Center provided reverse-phase protein array analysis. The core facility is supported by NIH Cancer Center Support Grant CA016672 through the MD Anderson Cancer Center.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014
Y1 - 2014
N2 - In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified lncRNA on chromosome 1 (FAL1), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1-specific siRNAs significantly inhibit tumor growth invivo.
AB - In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified lncRNA on chromosome 1 (FAL1), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1-specific siRNAs significantly inhibit tumor growth invivo.
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U2 - 10.1016/j.ccr.2014.07.009
DO - 10.1016/j.ccr.2014.07.009
M3 - Article
C2 - 25203321
AN - SCOPUS:84908671045
SN - 1535-6108
VL - 26
SP - 344
EP - 357
JO - Cancer Cell
JF - Cancer Cell
IS - 3
ER -