Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription  

作　　者：Sai-Nan Li Shan Yang Hao-Qi Wang Tian-Li Hui Meng Cheng Xi Zhang Bao-Kun Li Gui-Ying Wang 

机构地区：[1]The First Department of Surgery,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,Hebei Province,China [2]The Second Department of Surgery,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,Hebei Province,China [3]Department of General Surgery,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第4期1564-1577,共14页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Supported by Hebei Provincial Health Commission Youth Science and Technology Project,No.20210027.

摘　　要：BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC prog

关 键 词：Colorectal cancer Oxaliplatin resistance Prion protein testis specific Zinc finger protein 184 Homeodomain interacting protein kinase 2 

分 类 号：R735.34[医药卫生—肿瘤]