2. Academic Validation
  3. BRD4 drives esophageal squamous cell carcinoma growth by promoting RCC2 expression

BRD4 drives esophageal squamous cell carcinoma growth by promoting RCC2 expression

  • Oncogene. 2022 Jan;41(3):347-360. doi: 10.1038/s41388-021-02099-4.
Qiong Wu  # 1 2,  Fangfang Liu  # 1 2,  Mengmeng Ge 2,  Kyle Vaughn Laster 2,  Lixiao Wei 2,  Ruijuan Du 1 2,  Ming Jiang 2,  Jing Zhang 1 2,  Yafei Zhi 1 2,  Guoguo Jin 2 3,  Simin Zhao 2 4,  Dong Joon Kim 5 6,  Zigang Dong 7 8 9 10,  Kangdong Liu 11 12 13 14 15
Affiliations

Affiliations

  • 1 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
  • 2 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China.
  • 3 The Henan Luoyang Orthopedic Hospital, Zhengzhou, 450000, Henan, China.
  • 4 Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.
  • 5 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China. djkim@hci-cn.org.
  • 6 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China. djkim@hci-cn.org.
  • 7 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China. zgdong@hci-cn.org.
  • 8 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China. zgdong@hci-cn.org.
  • 9 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450000, Henan, China. zgdong@hci-cn.org.
  • 10 Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, 450000, Henan, China. zgdong@hci-cn.org.
  • 11 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
  • 12 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China. kdliu@zzu.edu.cn.
  • 13 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, 450000, Henan, China. kdliu@zzu.edu.cn.
  • 14 Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, 450000, Henan, China. kdliu@zzu.edu.cn.
  • 15 Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, 450000, Henan, China. kdliu@zzu.edu.cn.
  • # Contributed equally.
PMID: 34750516 DOI: 10.1038/s41388-021-02099-4
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.

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