The role of histone H1.2 in pancreatic cancer metastasis and chemoresistance
作者全名："Gu, Jianyou; Zhang, Junfeng; Xia, Renpei; Wang, Xianxing; Yang, Jiali; Xie, Fuming; Zhou, Qiang; Li, Jinghe; Zhang, Tao; Chen, Qing; Fan, Yingfang; Guo, Shixiang; Wang, Huaizhi"
作者地址："[Gu, Jianyou; Zhang, Junfeng; Xia, Renpei; Wang, Xianxing; Yang, Jiali; Xie, Fuming; Zhou, Qiang; Li, Jinghe; Zhang, Tao; Chen, Qing; Guo, Shixiang; Wang, Huaizhi] Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, Chongqing, Peoples R China; [Gu, Jianyou; Zhang, Junfeng; Zhang, Tao; Wang, Huaizhi] Chongqing Med Univ, Univ Chinese Acad Sci UCAS, Chongqing Sch, Chongqing, Peoples R China; [Fan, Yingfang; Wang, Huaizhi] Southern Med Univ, Dept Biliary Surg, Affiliated Hosp 3, Guangzhou 510630, Peoples R China; [Wang, Xianxing; Zhang, Tao; Guo, Shixiang; Wang, Huaizhi] Chongqing Key Lab Intelligent Med Engn Hepatopancr, Chongqing 401147, Peoples R China; [Guo, Shixiang] Univ Chinese Acad Sci, Chongqing Sch, Chongqing 400714, Peoples R China"
通信作者："Guo, SX; Wang, HZ (通讯作者)，Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, Chongqing, Peoples R China.; Fan, YF; Wang, HZ (通讯作者)，Southern Med Univ, Dept Biliary Surg, Affiliated Hosp 3, Guangzhou 510630, Peoples R China."
来源：DRUG RESISTANCE UPDATES
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
WOS号：WOS:001169499100001
JCR分区：Q1
影响因子：15.8
年份：2024
卷号：73
期号：
开始页：
结束页：
文献类型：Article
关键词：H1-2; Chemoresistance; Metastasis; C-MYC; Pancreatic Cancer
摘要："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."
基金机构："National Natural Science Foundation of China [82072723, 82103249, 82203165]; Natural Science Foundation of Chongqing, China [CSTB2022NSCQ-MSX1339, CSTB2022NSCQ-MSX1273]; Chongqing Technology Innovation and Application Development Special Key Project [CSTB2022TIAD-KPX0170]"
基金资助正文："This work was sponsored by National Natural Science Foundation of China (No. 82203165) and Natural Science Foundation of Chongqing, China (No. CSTB2022NSCQ-MSX1273) for Jianyou Gu; Natural Science Foundation of Chongqing, China (No. CSTB2022NSCQ-MSX1339) for Junfeng Zhang; National Natural Science Foundation of China (NO. 82072723 and NO. 82103249) and Chongqing Technology Innovation and Application Development Special Key Project (No. CSTB2022TIAD-KPX0170) for Huaizhi Wang."
