Genomic destabilization and defective DNA repair are the most prominent features of tumour cells and are exploited by various chemotherapy drugs for cancer therapy.Long non-coding RNA(lncR-NAs)have emerged as powerful...Genomic destabilization and defective DNA repair are the most prominent features of tumour cells and are exploited by various chemotherapy drugs for cancer therapy.Long non-coding RNA(lncR-NAs)have emerged as powerful regulators of gene expression and are thus involved in diverse biological processes.Recent studies have demonstrated that several lncRNAs play critical roles in DNA repair.Nonetheless,the relationship between DNA damage-responsive lncRNAs and chemoresistance remains poorly defined.In this study,we established four different DNA damage models triggered by cisplatin(DDP),H2O2,neocarzinostatin(NCS)or ultraviolet(UV)irradiation and identified a specific upregu-lated lncRNA(lnc-DUSP6)involved in the cisplatin-induced DNA damage response.Furthermore,loss-or gain-of-function experiments confirmed that lnc-DUSP6 enhanced DNA repair and cell survival under cisplatin treatment,thus promoting cisplatin resistance.Mechanistically,an RNA immunoprecipitation(RIP)assay revealed that lnc-DUSP6 directly interacts with DUSP6(Dual Specificity Phosphatase 6),which is closely associated with cisplatin sensitivity.Additionally,overexpression of DUSP6 significantly rescued the effects of lnc-DUSP6 silencing on DNA repair and cell survival under cisplatin treatment.O-verall,our results show the effect and underlying mechanism of lnc-DUSP6 in cisplatin resistance:lnc-DUSP6 promotes cisplatin-induced DNA damage repair and cisplatin resistance by stabilizing DUSP6,which is highly clinically important for enhancing the efficacy of cisplatin for cancers.展开更多
目的:探讨虎黄洗剂对糖尿病创面愈合的影响及作用机制。方法:通过中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库查询虎黄洗剂各组分的有效成分及靶基...目的:探讨虎黄洗剂对糖尿病创面愈合的影响及作用机制。方法:通过中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库查询虎黄洗剂各组分的有效成分及靶基因。通过比较毒理基因组学数据库(Comparative Toxicogenomics Database,CTD)及GeneCards数据库筛选糖尿病足疾病靶点。采用Cytoscape软件构建成分-靶点相互作用网络。使用DAVID在线工具进行基因本体(gene ontology,GO)及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。对糖尿病大鼠创面组织采用转录组学测序分析。动物实验验证虎黄洗剂对糖尿病大鼠创面愈合的影响,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测创面组织炎症因子白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α及IL-1β表达。结果:网络药理学及转录组学测序分析表明,虎黄洗剂潜在靶点与炎症调控密切相关。创面局部应用虎黄洗剂可促进糖尿病创面愈合,苏木精-伊红(hematoxylin and eosin,HE)染色结果显示虎黄洗剂可促进糖尿病创面上皮化,ELISA检测结果提示虎黄洗剂可抑制创面组织炎症因子IL-6、TNF-α及IL-1β表达。结论:虎黄洗剂可抑制糖尿病创面炎症反应,促进创面愈合。展开更多
基金Supported by the National Natural Science Foundation of China(No.82071571)the Natural Science Foundation of Guangdong Province(No.2021A1515010601)+3 种基金Guangdong Provincial Basic and Applied Basic Research Foundation-Dongguan Joint Fund(No.2024A1515140121)the“Climbing”Program of Guangdong Province(No.pdjh2021b0226)the Innovation and Entrepreneurship Program for College Students(No.GDMU2022038,202310571038,ZZDC002,S202510571041)Guangdong Medical University Undergraduate Innovation and Entrepreneurship Education Base Project(No.JDXM2024039,JDXM2025046)。
文摘Genomic destabilization and defective DNA repair are the most prominent features of tumour cells and are exploited by various chemotherapy drugs for cancer therapy.Long non-coding RNA(lncR-NAs)have emerged as powerful regulators of gene expression and are thus involved in diverse biological processes.Recent studies have demonstrated that several lncRNAs play critical roles in DNA repair.Nonetheless,the relationship between DNA damage-responsive lncRNAs and chemoresistance remains poorly defined.In this study,we established four different DNA damage models triggered by cisplatin(DDP),H2O2,neocarzinostatin(NCS)or ultraviolet(UV)irradiation and identified a specific upregu-lated lncRNA(lnc-DUSP6)involved in the cisplatin-induced DNA damage response.Furthermore,loss-or gain-of-function experiments confirmed that lnc-DUSP6 enhanced DNA repair and cell survival under cisplatin treatment,thus promoting cisplatin resistance.Mechanistically,an RNA immunoprecipitation(RIP)assay revealed that lnc-DUSP6 directly interacts with DUSP6(Dual Specificity Phosphatase 6),which is closely associated with cisplatin sensitivity.Additionally,overexpression of DUSP6 significantly rescued the effects of lnc-DUSP6 silencing on DNA repair and cell survival under cisplatin treatment.O-verall,our results show the effect and underlying mechanism of lnc-DUSP6 in cisplatin resistance:lnc-DUSP6 promotes cisplatin-induced DNA damage repair and cisplatin resistance by stabilizing DUSP6,which is highly clinically important for enhancing the efficacy of cisplatin for cancers.
文摘目的:探讨虎黄洗剂对糖尿病创面愈合的影响及作用机制。方法:通过中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库查询虎黄洗剂各组分的有效成分及靶基因。通过比较毒理基因组学数据库(Comparative Toxicogenomics Database,CTD)及GeneCards数据库筛选糖尿病足疾病靶点。采用Cytoscape软件构建成分-靶点相互作用网络。使用DAVID在线工具进行基因本体(gene ontology,GO)及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。对糖尿病大鼠创面组织采用转录组学测序分析。动物实验验证虎黄洗剂对糖尿病大鼠创面愈合的影响,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测创面组织炎症因子白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α及IL-1β表达。结果:网络药理学及转录组学测序分析表明,虎黄洗剂潜在靶点与炎症调控密切相关。创面局部应用虎黄洗剂可促进糖尿病创面愈合,苏木精-伊红(hematoxylin and eosin,HE)染色结果显示虎黄洗剂可促进糖尿病创面上皮化,ELISA检测结果提示虎黄洗剂可抑制创面组织炎症因子IL-6、TNF-α及IL-1β表达。结论:虎黄洗剂可抑制糖尿病创面炎症反应,促进创面愈合。
