PDF(Pubmed)
Abstract：
Gastrointestinal (GI) cancers are some of the main public health threats to the world. Even though surgery, chemotherapy, and targeted therapy are available for their treatments, these approaches provide limited success in reducing mortality, making the identification of additional therapeutic targets mandatory. Chromatin remodeling in cancer has long been studied and related therapeutics are widely used, although less is known about factors with prognostic and therapeutic potential in such areas as gastrointestinal cancers. Through applying systematic bioinformatic analysis, we determined that out of 31 chromatin remodeling factors in six gastrointestinal cancers, only PR/SET domain 1 (PRDM1) showed both expression alteration and prognosis prediction. Analyses on pathways, therapies, and mediators showed that cell cycle, bromodomain inhibitor IBET151, and BET protein BRD4 were, respectively involved in PRDM1-high stomach cancer, while cell line experiments validated that PRDM1 knockdown in human stomach cancer cell line SNU-1 decreased its proliferation, BRD4 expression, and responsiveness to IBET151; accordingly, these results indicate the contribution by PRDM1 in stomach cancer formation and its association with BRD4 modulation as well as BET inhibitor treatment.
摘要：
胃肠道（GI）癌症是世界上一些主要的公共卫生威胁。即使手术，化疗,靶向治疗可用于他们的治疗，这些方法在降低死亡率方面取得的成功有限，强制确定额外的治疗目标。癌症中的染色质重塑已经被研究了很长时间，相关疗法被广泛使用。尽管对胃肠道癌症等领域具有预后和治疗潜力的因素知之甚少。通过应用系统的生物信息学分析，我们确定在6种胃肠道肿瘤的31种染色质重塑因子中，只有PR/SET结构域1（PRDM1）显示表达改变和预后预测。对途径的分析，疗法,介体显示细胞周期，溴结构域抑制剂IBET151和BET蛋白BRD4，分别参与PRDM1高胃癌，虽然细胞系实验验证了PRDM1在人胃癌细胞系SNU-1中的敲除降低了其增殖，BRD4表达式，以及对IBET151的响应；因此，这些结果表明PRDM1在胃癌形成中的作用及其与BRD4调节以及BET抑制剂治疗的相关性.
