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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Kidney Cancer | Research article

Ubiquitous expressed transcript promotes tumorigenesis by acting as a positive modulator of the polycomb repressive complex 2 in clear cell renal cell carcinoma

Authors: Jin Zeng, Wei Xiang, Yucong Zhang, Chunhua Huang, Ke Chen, Zhiqiang Chen

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

The ubiquitous expressed transcript (UXT) plays a key role in various tumors by regulating transcriptional activity of multiple transcription factors, including androgen receptor (AR). However, the role of UXT in clear cell renal cell carcinoma (ccRCC) is still unknown.

Methods

Yeast two-hybrid screening, GST pull-down and co-immunoprecipitation assays were performed to detect the interacting protein of UXT. Chromatin immunoprecipitation (ChIP) was performed to investigate the levels of histone H3 lysine 27 trimethylation at the HOXA9 promoters. CCK-8 assays, colony formation assays and Transwell assays were performed to detect the proliferation, colony formation, migration and invasion of renal cancer cells. Quantitative PCR analysis was performed to detect the expressions of UXT in human ccRCC samples.

Results

The enhancer of zeste homolog 2 (EZH2) is a novel UXT interacting protein and UXT interacts with EZH2 in the nucleus. In addition, UXT interacts with the polycomb repressive complex 2 (PRC2) through directly binding to EZH2 and suppressor of zeste 12 homolog (SUZ12), but not to embryonic ectoderm development (EED). Moreover, the UXT activates EZH2 histone methyltransferase activity by facilitating EZH2 binding with SUZ12. We further provided striking evidences that knockdown of UXT inhibits proliferation, colony formation, migration and invasion of renal cancer cells, in an EZH2-dependent manner. Importantly, the upregulation of UXT expression was observed in clinical ccRCC samples, and the high expression level of UXT was associated with advanced stage, distant metastasis and poor overall survival in patients with ccRCC.

Conclusion

The UXT is a novel regulator of the PRC2 and acts as a renal cancer oncogene that affects the progression and survival of ccRCC patients.
Appendix
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Metadata
Title
Ubiquitous expressed transcript promotes tumorigenesis by acting as a positive modulator of the polycomb repressive complex 2 in clear cell renal cell carcinoma
Authors
Jin Zeng
Wei Xiang
Yucong Zhang
Chunhua Huang
Ke Chen
Zhiqiang Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-6069-3

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