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

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Zhang, E-b, Yin, D-d, Sun, M, Kong, R, Liu, X-h, You, L-h, Han, L, Xia, R, Wang, K-m, Yang, J-s, De, W, Shu, Y-q, Wang, Z-x·2014·Cell Death & Disease
DOI 10.1038/cddis.2014.201
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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.

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Metadata

Authors
Zhang, E.-B., Yin, D.-D., Sun, M., Kong, R., Liu, X.-H., You, L.-H., Han, L., Xia, R., Wang, K.-M., Yang, J.-S., De, W., Shu, Y.-Q., & Wang, Z.-X.
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2014-05-22
Volume
5
Issue
5
Pages
e1243-e1243
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/cddis.2014.201
OpenAlex
W1966397536
Cited by
427
References
4
FWCI
17.30
Type
journal article
Language
en
Open access
gold
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CoChat. (2026). Citation check: P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. https://app.cochat.ai/papers/10.1038/cddis.2014.201
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Zhang, E.-B., Yin, D.-D., Sun, M., Kong, R., Liu, X.-H., You, L.-H., Han, L., Xia, R., Wang, K.-M., Yang, J.-S., De, W., Shu, Y.-Q., & Wang, Z.-X. (2014). P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death & Disease. https://doi.org/10.1038/cddis.2014.201

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