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BAP18 is involved in upregulation of CCND1/2 transcription to promote cell growth in oral squamous cell carcinoma.
EBioMedicine ( IF 9.7 ) Pub Date : 2020-02-26 , DOI: 10.1016/j.ebiom.2020.102685
Xue Wang 1 , Chunyu Wang 2 , Guangqi Yan 3 , Yuanyuan Kang 4 , Ge Sun 2 , Shengli Wang 2 , Renlong Zou 2 , Hongmiao Sun 2 , Kai Zeng 2 , Huijuan Song 2 , Wei Liu 2 , Ning Sun 2 , Wensu Liu 2 , Yue Zhao 2
Affiliation  

BACKGROUND As a reader of histone H3K4me3, BPTF associated protein of 18 kDa (BAP18) is involved in modulation of androgen receptor action in prostate cancer. However, the function of BAP18 on oral squamous cell carcinoma (OSCC) and its molecular mechanism remains to be elusive. METHODS OSCC-derived cell lines carrying silenced BAP18 were established by Lentiviral infection. Quantitative PCR (qPCR), western blot, and ChIP assay were performed to detect gene transcription regulation and the possible mechanism. Colony formation, cell growth curve and xenograft tumor experiments were performed to examine cell growth and proliferation. FINDINGS Our study demonstrated that BAP18 was highly expressed in OSCC samples compared with that in benign. BAP18 depletion obviously influenced the expression of a series of genes, including cell cycle-related genes. We thus provided the evidence to demonstrate that BAP18 depletion significantly decreases CCND1 and CCND2 (CCND1/2) transcription. In addition, BAP18 is recruited to the promoter regions of CCND1/2, thereby facilitating the recruitment of the core subunits of MLL1 complex to the same regions, to increase histone H3K4me3 levels. Furthermore, BAP18 depletion delayed G1-S phase transition and inhibited cell growth in OSCC-derived cell lines. INTERPRETATION This study suggests that BAP18 is involved in modulation of CCND1/2 transcription and promotes OSCC progression. BAP18 could be a potential target for OSCC treatment and diagnosis. FUND: This work was funded by National Natural Science Foundation of China (31871286, 81872015, 31701102, 81702800, 81902889), Foundation for Special Professor of Liaoning Province, and Supported project for young technological innovation-talents in Shenyang (No. RC170541).

中文翻译:

BAP18参与CCND1 / 2转录的上调,以促进口腔鳞状细胞癌中的细胞生长。

背景技术作为组蛋白H3K4me3的读者,BPTF相关蛋白18kDa(BAP18)参与前列腺癌中雄激素受体作用的调节。但是,BAP18在口腔鳞状细胞癌(OSCC)中的功能及其分子机制尚不清楚。方法通过慢病毒感染建立携带沉默BAP18的OSCC细胞系。进行了定量PCR(qPCR),蛋白质印迹和ChIP分析,以检测基因转录调控及其可能的机制。进行菌落形成,细胞生长曲线和异种移植肿瘤实验以检查细胞生长和增殖。结果我们的研究表明,与良性相比,BAP18在OSCC样品中高表达。BAP18耗竭显然影响了一系列基因的表达,包括与细胞周期相关的基因。因此,我们提供了证据证明BAP18耗竭显着降低CCND1和CCND2(CCND1 / 2)转录。此外,BAP18被募集到CCND1 / 2的启动子区域,从而有助于将MLL1复合物的核心亚基募集到相同的区域,以增加组蛋白H3K4me3的水平。此外,BAP18消耗延迟了OSCC衍生细胞系中的G1-S相变并抑制了细胞生长。解释这项研究表明BAP18参与CCND1 / 2转录的调节并促进OSCC进程。BAP18可能是OSCC治疗和诊断的潜在目标。基金:这项工作由国家自然科学基金(31871286,81872015,31701102,81702800,81902889),辽宁省特聘教授基金资助,
更新日期:2020-02-27
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