2. Academic Validation
  3. BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer

BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer

  • Cell Death Dis. 2018 May 1;9(5):519. doi: 10.1038/s41419-018-0536-7.
Weihong Niu 1 2 3,  Yanwei Luo 2 3,  Xinye Wang 2 3,  Yao Zhou 2 3,  Hui Li 4,  Heran Wang 1 3,  Yaojie Fu 5,  Shanshan Liu 5,  Shanghelin Yin 5,  Jianglei Li 5,  Ran Zhao 2 3,  Yukun Liu 2 3,  Songqing Fan 4,  Zheng Li 2 3 6,  Wei Xiong 2 3,  Xiaoling Li 2 3,  Guiyuan Li 1 2 3,  Caiping Ren 3,  Ming Tan 7,  Ming Zhou 8 9 10
Affiliations

Affiliations

  • 1 The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, 410013, People's Republic of China.
  • 2 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China.
  • 3 Cancer Research Institute, Central South University, Changsha, Hunan, 410078, People's Republic of China.
  • 4 The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410011, People's Republic of China.
  • 5 Medical school of Xiangya, Central South University, Changsha, Hunan, 410013, People's Republic of China.
  • 6 High Resolution Mass Spectrometry Laboratory of Advanced Research Center, Central South University, Changsha, Hunan, 410013, People's Republic of China.
  • 7 Mitchell Cancer Institute, University of South Alabama, Mobile, AL, 36604, USA. mtan@health.southalabama.edu.
  • 8 The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, 410013, People's Republic of China. zhouming2001@163.com.
  • 9 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China. zhouming2001@163.com.
  • 10 Cancer Research Institute, Central South University, Changsha, Hunan, 410078, People's Republic of China. zhouming2001@163.com.
PMID: 29725006 DOI: 10.1038/s41419-018-0536-7
Abstract

The bromodomain-containing protein 7 (BRD7) was first identified as a tumor suppressor in nasopharyngeal carcinoma and has critical roles in Cancer development and progression. However, the regulatory roles and mechanisms of BRD7 in Cancer metabolism are still unknown. In this study, we demonstrated that BRD7 was lowly expressed in breast Cancer tissues and was identified as a poor prognostic factor in breast Cancer. Meanwhile, BRD7 could suppress cell proliferation, initiate cell Apoptosis and reduce aerobic glycolysis, suggesting that BRD7 plays a tumor suppressive roles in breast Cancer. Mechanistically, BRD7 could negatively regulate a critical glycolytic Enzyme LDHA through directly interaction with its upstream transcription factor, HIF1α, facilitating degradation of HIF1α mediated by ubiquitin-proteasome pathway. Moreover, restoring the expression of LDHA in breast Cancer cells could reverse the effect of BRD7 on aerobic glycolysis, cell proliferation, and tumor formation, as well as the expression of cell cycle and apopotosis related molecules such as cyclin D1, CDK4, P21, and c-PARP both in vitro and in vivo. Taken together, these results indicate that BRD7 acts as a tumor suppressor in breast Cancer and represses the glycolysis and tumor progression through inactivation of HIF1α/LDHA transcription axis.

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