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

    237 Scopus citations

    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 - Jan 1 2014

    ASJC Scopus subject areas

    • Oncology
    • Cell Biology
    • Cancer Research

    Fingerprint Dive into the research topics of 'A Functional Genomic Approach Identifies FAL1 as an Oncogenic Long Noncoding RNA that Associates with BMI1 and Represses p21 Expression in Cancer'. Together they form a unique fingerprint.

  • Cite this

    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