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

被引：508

作者：

Hu, Xiaowen ^{[1
,2
,3
]}

Feng, Yi ^{[4
]}

Zhang, Dongmei ^{[1
,2
,8
]}

Zhao, Sihai D. ^{[10
]}

Hu, Zhongyi ^{[1
,2
]}

Greshock, Joel ^{[4
]}

Zhang, Youyou ^{[1
,2
]}

Yang, Lu ^{[1
,2
,9
]}

Zhong, Xiaomin ^{[1
,2
,11
]}

Wang, Li-Ping ^{[5
]}

Jean, Stephanie ^{[3
]}

Li, Chunsheng ^{[1
,2
]}

Huang, Qihong ^{[12
]}

Katsaros, Dionyssios ^{[13
]}

Montone, Kathleen T. ^{[5
]}

Tanyi, Janos L. ^{[3
]}

Lu, Yiling ^{[15
]}

Boyd, Jeff ^{[14
]}

Nathanson, Katherine L. ^{[6
]}

Li, Hongzhe ^{[7
]}

Mills, Gordon B. ^{[15
]}

Zhang, Lin ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA

[4] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[5] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[7] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[8] Sichuan Univ, West China Med Sch, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[9] Sichuan Univ, West China Med Sch, Dept Obstet & Gynecol, Chengdu 610041, Peoples R China

[10] Univ Illinois, Dept Stat, Champaign, IL 61820 USA

[11] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Biol, Ctr Stem Biol & Tissue Engn, Guangzhou 510080, Guangdong, Peoples R China

[12] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA

[13] Univ Turin, Dept Obstet & Gynecol, I-10124 Turin, Italy

[14] Fox Chase Canc Ctr, Canc Genome Inst, Philadelphia, PA 19111 USA

[15] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX USA

来源：

CANCER CELL | 2014年 / 26卷 / 03期

关键词：

GENE ACTIVATION PROGRAMS; COPY-NUMBER ALTERATION; PROSTATE-CANCER; MESSENGER-RNAS; HUMAN-CELLS; XIST RNA; TRANSCRIPTION; METASTASIS; ENHANCERS; EVOLUTION;

D O I：

10.1016/j.ccr.2014.07.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (IncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of IncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of IncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified IncRNA 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.

引用

页码：344 / 357

页数：14

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