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Cell Death Dis. 2014 May 22;5:e1243. doi: 10.1038/cddis.2014.201.

P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression.

Author information

1
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
2
Central Laboratory, Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, China.
3
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
4
Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
5
Department of Oncology, Affiliated Nanjing Hospital of Nanjing Medical Univeraity, Nanjing, Jiangsu, China.

Abstract

Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy.

PMID:
24853421
PMCID:
PMC4047917
DOI:
10.1038/cddis.2014.201
[Indexed for MEDLINE]
Free PMC Article

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