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

Xiaowen Hu, Yi Feng, Dongmei Zhang, Sihai D. Zhao, Zhongyi Hu, Joel Greshock, Youyou Zhang, Lu Yang, Xiaomin Zhong, Li Ping Wang, Stephanie Jean, Chunsheng Li, Qihong Huang, Dionyssios Katsaros, Kathleen T. Montone, Janos L. Tanyi, Yiling Lu, Jeff Boyd, Katherine L. Nathanson, Hongzhe LiGordon B. Mills, Lin Zhang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)344-357
Number of pages14
JournalCancer Cell
Volume26
Issue number3
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Hu, X., Feng, Y., Zhang, D., Zhao, S. D., Hu, Z., Greshock, J., Zhang, Y., Yang, L., Zhong, X., Wang, L. P., Jean, S., Li, C., Huang, Q., Katsaros, D., Montone, K. T., Tanyi, J. L., Lu, Y., Boyd, J., Nathanson, K. L., ... Zhang, L. (2014). A Functional Genomic Approach Identifies FAL1 as an Oncogenic Long Noncoding RNA that Associates with BMI1 and Represses p21 Expression in Cancer. Cancer Cell, 26(3), 344-357. https://doi.org/10.1016/j.ccr.2014.07.009