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 Li; Gordon B Mills; Lin Zhang

doi:10.1016/j.ccr.2014.07.009

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 journal › Article › peer-review

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 in vivo.

Original language	English
Journal	Cancer Cell
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2014.07.009
Publication status	Published - 8 Sept 2014
Externally published	Yes

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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). https://doi.org/10.1016/j.ccr.2014.07.009

@article{5e9192461c9f4a19ad707ac64638147a,

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

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 in vivo.",

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

year = "2014",

month = sep,

day = "8",

doi = "10.1016/j.ccr.2014.07.009",

language = "English",

volume = "26",

journal = "Cancer Cell",

issn = "1878-3686",

publisher = "Cell Press",

number = "3",

}

Hu, X, Feng, Y, Zhang, D, Zhao, SD, Hu, Z, Greshock, J, Zhang, Y, Yang, L, Zhong, X, Wang, L-P, Jean, S, Li, C, Huang, Q, Katsaros, D, Montone, KT, Tanyi, JL, Lu, Y, Boyd, J, Nathanson, KL, Li, H, Mills, GB & 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, vol. 26, no. 3. https://doi.org/10.1016/j.ccr.2014.07.009

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

PY - 2014/9/8

Y1 - 2014/9/8

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 in vivo.

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 in vivo.

U2 - 10.1016/j.ccr.2014.07.009

DO - 10.1016/j.ccr.2014.07.009

M3 - Article

C2 - 25203321

SN - 1878-3686

VL - 26

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

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

Abstract

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