Brd4 drives esophageal squamous cell carcinoma growth by promoting rcc2 expression

ABSTRACT The low survival rate of esophageal squamous cell carcinoma patients is primarily attributed to technical limitations and a lack of insight regarding the molecular mechanisms

contributing to its progression. Alterations in epigenetic modulators are critical to cancer development and prognosis. BRD4, a chromatin reader protein, plays an essential role in

regulating oncogene expression. Here, we investigated the contributing role of BRD4 and its related mechanisms in the context of ESCC tumor progression. Our observations showed that BRD4

transcript and protein expression levels are significantly increased in ESCC patient tissues. Genetic or pharmacological inhibition of BRD4 suppressed ESCC cell proliferation in vitro and in

vivo. Proteomic and transcriptomic analyses were subsequently used to deduce the potential targets of BRD4. Mechanistic studies showed that RCC2 is a downstream target of BRD4. Inhibition

of either BRD4 or RCC2 resulted in decreased ESCC cell proliferation. The BRD4-TP73 interaction facilitated the binding of BRD4 complex to the promoter region of RCC2, and subsequently

modulated RCC2 transcription. Furthermore, targeting BRD4 with inhibitors significantly decreased tumor volume in ESCC PDX models, indicating that BRD4 expression may contribute to tumor

progression. Collectively, these findings suggest that BRD4 inhibition could be a promising strategy to treat ESCC by downregulating RCC2. Access through your institution Buy or subscribe

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TAB182 AGGRAVATES PROGRESSION OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA BY ENHANCING Β-CATENIN NUCLEAR TRANSLOCATION THROUGH FHL2 DEPENDENT MANNER Article Open access 26 October 2022 BROMODOMAIN

PROTEIN BRDT DIRECTS ΔNP63 FUNCTION AND SUPER-ENHANCER ACTIVITY IN A SUBSET OF ESOPHAGEAL SQUAMOUS CELL CARCINOMAS Article Open access 03 March 2021 BAF53A DRIVES COLORECTAL CANCER

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2016;35:785–92. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This research was funded by the National Natural Science Foundations of China (Grant no. 81872335),

National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China (No. 2018ZX09711002) and Central Plains Science and Technology Innovation Leading

Talents (KL). We thank all members of our team for critical input and suggestions. AUTHOR INFORMATION Author notes * These authors contributed equally: Qiong Wu, Fangfang Liu AUTHORS AND

AFFILIATIONS * The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China Qiong Wu, Fangfang Liu, Ruijuan Du, Jing Zhang, Yafei Zhi,

 Dong Joon Kim, Zigang Dong & Kangdong Liu * China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China Qiong Wu, Fangfang Liu, Mengmeng Ge, Kyle Vaughn Laster, Lixiao Wei, 

Ruijuan Du, Ming Jiang, Jing Zhang, Yafei Zhi, Guoguo Jin, Simin Zhao, Dong Joon Kim, Zigang Dong & Kangdong Liu * The Henan Luoyang Orthopedic Hospital, Zhengzhou, 450000, Henan, China

Guoguo Jin * Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China Simin Zhao * State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou,

450000, Henan, China Zigang Dong & Kangdong Liu * Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, 450000, Henan, China Zigang Dong 

& Kangdong Liu * Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, 450000, Henan, China Kangdong Liu Authors * Qiong Wu View author publications You can also

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inPubMed Google Scholar CONTRIBUTIONS QW designed and performed the most of experiments and the data analysis; FL, MG and LW helped in animal experimentation; KVL took charge of

bioinformatics analyses; QW and KVL prepared and revised the manuscript; RD, MJ, GJ, and SZ provided technique supports; JZ and YZ helped perform in vitro assays. DJK and ZD supervise the

overall experimental design. KL designed and supervised the study; All authors read and approved the final manuscript. CORRESPONDING AUTHORS Correspondence to Dong Joon Kim, Zigang Dong or

Kangdong Liu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ETHICAL APPROVAL This study was approved by the Ethics Committee of Zhengzhou University.

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_Oncogene_ 41, 347–360 (2022). https://doi.org/10.1038/s41388-021-02099-4 Download citation * Received: 08 April 2021 * Revised: 18 October 2021 * Accepted: 25 October 2021 * Published: 08

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