Jianyou Gu , Junfeng Zhang , Renpei Xia , Xianxing Wang , Jiali Yang , Fuming Xie , Qiang Zhou , Jinghe Li , Tao Zhang , Qing Chen , Yingfang Fan , Shixiang Guo , Huaizhi Wang
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引用次数: 0
摘要
胰腺癌是一种高度转移的消化系统恶性肿瘤。耐药是癌症治疗过程中常见的现象。本研究旨在探讨前列腺癌化疗耐药与肿瘤转移的关系及其可能的分子和细胞机制。方法利用PC基因表达数据，建立基于转移和化疗耐药相关基因的MCS (Metastasis and chemresistant Signature，转移和化疗耐药特征)评分系统并进行验证，并将该模型应用于单细胞RNA测序数据。通过增殖、侵袭、迁移、药物敏感性、救援实验和免疫组化等体外和体内实验，探讨连接蛋白H1.2 (H1-2)对PC的影响，强调其与c-MYC信号通路的调控作用。结果一种新的MCS评分系统准确预测了PC患者的生存，并与PC单细胞RNA测序数据中的化疗耐药和上皮-间质转化(EMT)相关。H1-2成为重要的预后因素，其高表达表明化疗耐药和EMT增加。这种上调是由c-MYC介导的，c-MYC也被发现在PC组织中高度表达。结论MCS评分系统对前列腺癌的化疗耐药和转移潜力有重要意义。以H1-2为靶点可改善PC患者的治疗策略和预后。
The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance
Aims
Pancreatic cancer (PC) is a highly metastatic malignant tumor of the digestive system. Drug resistance frequently occurs during cancer treatment process. This study aimed to explore the link between chemoresistance and tumor metastasis in PC and its possible molecular and cellular mechanisms.
Methods
A Metastasis and Chemoresistance Signature (MCS) scoring system was built and validated based on metastasis- and chemoresistance-related genes using gene expression data of PC, and the model was applied to single-cell RNA sequencing data. The influence of linker histone H1.2 (H1–2) on PC was explored through in vitro and in vivo experiments including proliferation, invasion, migration, drug sensitivity, rescue experiments and immunohistochemistry, emphasizing its regulation with c-MYC signaling pathway.
Results
A novel MCS scoring system accurately predicted PC patient survival and was linked to chemoresistance and epithelial-mesenchymal transition (EMT) in PC single-cell RNA sequencing data. H1–2 emerged as a significant prognostic factor, with its high expression indicating increased chemoresistance and EMT. This upregulation was mediated by c-MYC, which was also found to be highly expressed in PC tissues.
Conclusion
The MCS scoring system offers insights into PC chemoresistance and metastasis potential. Targeting H1–2 could enhance therapeutic strategies and improve PC patient outcomes.
期刊介绍：
Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation.
Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective.
*Expert reviews in clinical and basic drug resistance research in oncology and infectious disease
*Describes emerging technologies and therapies, particularly those that overcome drug resistance
*Emphasises common themes in microbial and cancer research
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