Inhibition of bromodomain regulates cellular senescence in pancreatic adenocarcinoma.

IF 1.1 Q4 ONCOLOGY

International journal of clinical and experimental pathology Pub Date : 2024-10-15 eCollection Date: 2024-01-01 DOI:10.62347/BKNQ9812

Xiang Chen, Tao Yu, Shu Li, Hongcai Fang

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Abstract

Background: Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators that promote the transcription of genes in the chromatin region associated with acetylated histones. Small molecule BET inhibitor JQ1 suppresses the biologic function of BET proteins in a variety of tumors and inhibits their proliferation.

Methods: We investigated the effect of JQ1 in the treatment of pancreatic cancer. In addition, we evaluated the expression level of BRD4 protein in pancreatic cancer tissues using the Gene Expression Profiling Interactive Analysis (GEPIA) and the Human protein Altas databases and analyzed the correlation between BRD4 and the clinicopathologic features and immune checkpoints of pancreatic adenocarcinoma using UALACN and TIMER databases.

Results: JQ1 significantly inhibited the proliferation of pancreatic adenocarcinoma (PAAD) cells and induced cell senescence but had little effect on Senescence-associated secretory phenotype (SASP). Interestingly, JQ1 inhibited the epithelial-mesenchymal transition (EMT) and Wnt signaling pathways.

Conclusions: These results provide a theoretical basis for new targets in the treatment of pancreatic cancer.

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抑制溴化链可调节胰腺癌的细胞衰老。

背景：溴化多域和末端外域（BET）蛋白是重要的表观遗传调节因子，可促进与乙酰化组蛋白相关的染色质区域中基因的转录。小分子 BET 抑制剂 JQ1 可抑制 BET 蛋白在多种肿瘤中的生物功能并抑制其增殖：我们研究了 JQ1 治疗胰腺癌的效果。此外，我们还利用基因表达谱交互分析（GEPIA）和人类蛋白质 Altas 数据库评估了 BRD4 蛋白在胰腺癌组织中的表达水平，并利用 UALACN 和 TIMER 数据库分析了 BRD4 与胰腺癌临床病理特征和免疫检查点的相关性：结果：JQ1能明显抑制胰腺腺癌（PAAD）细胞的增殖并诱导细胞衰老，但对衰老相关分泌表型（SASP）影响甚微。有趣的是，JQ1 能抑制上皮-间质转化（EMT）和 Wnt 信号通路：这些结果为治疗胰腺癌的新靶点提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International journal of clinical and experimental pathology ONCOLOGY-PATHOLOGY

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0.00%

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审稿时长

1 months

期刊介绍： The International Journal of Clinical and Experimental Pathology (IJCEP, ISSN 1936-2625) is a peer reviewed, open access online journal. It was founded in 2008 by an international group of academic pathologists and scientists who are devoted to the scientific exploration of human disease and the rapid dissemination of original data. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal.