Jian Jiang, Tianci Shen, Dan Chen, Zihao Dai, Xuelong Wang, Qiang Meng, Zhuo Yang, Di Zhang, Xiaoyi Guo, Jianqiang Xu, Jiangning Gu, Changmiao Wang
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引用次数: 0
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid tumor; however, the barrier of chemoresistance has yet to be overcome for longer survival. Aberrant gene expression due to epigenetic modification plays an important role in tumorigenesis and treatment. Super enhancers are epigenetic elements that promote targeted gene transcription and ultimately lead to chemoresistance. This study found that the expression of FOXM1 was higher in PDAC tissues and negatively correlated with prognosis. Through RNA sequencing and chromatin immunoprecipitation-sequencing analyses, FOXM1 was found to be regulated by a BRD4-associated super enhancer, which finally promoted gemcitabine resistance via TGFβ/Smad signaling pathway activation. Both TGFβ/Smad-specific inhibitor LY364947 and the BRD4 inhibitor JQ1 decreased the IC50 value of gemcitabine in vitro. Furthermore, combined gemcitabine and JQ1 therapy could not only enhance the therapeutic effect of gemcitabine but also reverse drug resistance in vivo. In conclusion, the super enhancer-associated gene FOMX1 contributes to gemcitabine resistance and is a promising target in PDAC treatment.
期刊介绍：
Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems
The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized.
Examples of subject areas that CBB publishes are:
· biochemical and biophysical aspects of cell structure and function;
· interactions of cells and their molecular/macromolecular constituents;
· innovative developments in genetic and biomolecular engineering;
· computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies;
· photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design
For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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