title: Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer.
abstract: Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine (131)I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from (131)I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced (131)I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer.
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province, China; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Xinchao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Yusufu
authors.initials: Y
authors.lastname: Maimaiti
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province, China. Electronic address: gaobonn@163.com.
authors.forename: Zairong
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province, China.
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D009687:Nuclear Proteins / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D007457:Iodine Radioisotopes; D009687:Nuclear Proteins; D019275:Radiopharmaceuticals; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins
keywords: BRD4; C-MYC; JQ1; NIS; Thyroid cancer