Xinchao Wu1,2, Dong Liu1, Xuemei Gao2, Fei Xie1, Dan Tao3, Xingyuan Xiao1, Liang Wang1, Guosong Jiang1, Fuqing Zeng1. 1. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 3. Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, China.
Abstract
BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. RESULTS: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. CONCLUSIONS: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.
BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS:BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. RESULTS:BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. CONCLUSIONS: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.
Authors: Renata L Markman; Liana P Webber; Carlos H V Nascimento Filho; Leonardo A Reis; Pablo A Vargas; Marcio A Lopes; Virgilio Zanella; Manoela D Martins; Cristiane H Squarize; Rogerio M Castilho Journal: Cell Oncol (Dordr) Date: 2018-12-11 Impact factor: 6.730
Authors: Poonam Tewary; Alan D Brooks; Ya-Ming Xu; E M Kithsiri Wijeratne; Ashley L Babyak; Timothy C Back; Raj Chari; Christine N Evans; Curtis J Henrich; Thomas J Meyer; Elijah F Edmondson; Maria T Prudente de Aquino; Thanigaivelan Kanagasabai; Anil Shanker; A A Leslie Gunatilaka; Thomas J Sayers Journal: Cancer Res Date: 2021-04-09 Impact factor: 12.701