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A Functional Genomic Approach Identifies FAL1 as an Oncogenic Long Noncoding RNA that Associates with BMI1 and Represses p21 Expression in Cancer

2014; Cell Press; Volume: 26; Issue: 3 Linguagem: Inglês

10.1016/j.ccr.2014.07.009

1878-3686

Zhongyi Hu, Yi Feng, Dongmei Zhang, Sihai Dave Zhao, Zhongyi Hu, Joel Greshock, Youyou Zhang, Lu Yang, Xiaomin Zhong, Liping Wang, Stéphanie Jean, Chunsheng Li, Qihong Huang, Dionyssios Katsaros, Kathleen T. Montone, János L. Tanyi, Yiling Lu, Jeff Boyd, Katherine L. Nathanson, Hongzhe Li, Gordon B. Mills, Lin Zhang,

RNA Research and Splicing

Summary 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, f ocally a mplified l ncRNA 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 in vivo.