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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

BRD7 expression and c-Myc activation forms a double-negative feedback loop that controls the cell proliferation and tumor growth of nasopharyngeal carcinoma by targeting oncogenic miR-141

Authors: Yukun Liu, Ran Zhao, Yanmei Wei, Mengna Li, Heran Wang, Weihong Niu, Yao Zhou, Yuanzheng Qiu, Songqing Fan, Yihao Zhan, Wei Xiong, Yanhong Zhou, Xiaoling Li, Zheng Li, Guiyuan Li, Ming Zhou

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

miR-141 is up-regulated and plays crucial roles in nasopharyngeal carcinoma (NPC). However, the molecular mechanism underlying the dysregulation of miR-141 is still obscure.

Methods

Thus, the ChIP-PCR was performed to identify the c-Myc-binding sites in miR-141 and BRD7. qRT-PCR, western blot and immunohistochemistry assays were used to detect the expression of miR-141 and its up/down stream molecules. The rescue experiments on the c-Myc/miR-141 axis were performed in vitro and in vivo.

Results

Our results showed that the levels of mature miR-141, pre-miR-141 and pri-miR-141 were downregulated in c-Myc knockdown NPC cells. Meanwhile, c-Myc transactivates the expression of miR-141 by binding its promoter region. Moreover, BRD7 was identified as a co-factor of c-Myc to negatively regulate the activation of c-Myc/miR-141 axis, as well as a direct target of c-Myc. Moreover, restoration of miR-141 in c-Myc knockdown NPC cells notably rescued the effect of c-Myc on cell proliferation and tumor growth, as well as the blocking of PTEN/AKT pathway. Additionally, the expression of c-Myc was positively correlated with that of miR-141 and the clinical stages of NPC patients and negatively associated with the expression of BRD7. Our findings demonstrated that BRD7 expression and c-Myc activation forms a negative feedback loop to control the cell proliferation and tumor growth by targeting miR-141.

Conclusions

These observations provide new mechanistic insights into the dysregulation of miR-141 expression and a promising therapeutic option for NPC.
Appendix
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Metadata
Title
BRD7 expression and c-Myc activation forms a double-negative feedback loop that controls the cell proliferation and tumor growth of nasopharyngeal carcinoma by targeting oncogenic miR-141
Authors
Yukun Liu
Ran Zhao
Yanmei Wei
Mengna Li
Heran Wang
Weihong Niu
Yao Zhou
Yuanzheng Qiu
Songqing Fan
Yihao Zhan
Wei Xiong
Yanhong Zhou
Xiaoling Li
Zheng Li
Guiyuan Li
Ming Zhou
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0734-2

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