Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the d...Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.展开更多
基金supported by the Shandong Province Medical and Health Technology Project(202303111442).
文摘Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.
文摘目的探究肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)分子亚型特异性,为不同MIBC分子亚型患者的治疗提供指导。方法基于MIBC分子分型方法中的UNC分型法,应用转录组测序数据,将48例MIBC患者分为2种分子亚型即Basal型和Luminal型,并进行差异表达分析以探究MIBC特异性的lncRNAs,并进一步探讨其分子特征和临床意义。结合单细胞质谱流式细胞术(single-cell mass cytometry,CyTOF)和镜像质谱流式细胞术(imaging mass cytometry,IMC)分析MBNL1-AS1高表达组和低表达组Basal型MIBC患者的免疫微环境异质性。结果基于分子分型法筛选发现了在MIBC特异性表达的lncRNA MBNL1-AS1,其低表达与Basal型MIBC患者的不良预后密切相关(P=0.022)。且进一步分析转录组测序数据后发现,在Basal型MIBC中,MBNL1-AS1低表达组具有去分化(P=0.008)、高干性(P=0.020)和高增殖(P=0.010)的特征。MBNL1-AS1低表达组的Basal型MIBC患者的免疫评分与NK CD56bright细胞和Treg细胞的评分呈负相关(P<0.05),而MBNL1-AS1高表达组的B细胞和CD8+T细胞相关基因的表达水平较高。高维度单细胞蛋白质组学分析结果显示,MBNL1-AS1低表达的Basal型MIBC患者表现出较高的Treg细胞亚群丰度(P=0.016)。结论MBNL1-AS1低表达组的Basal型MIBC患者具有去分化、高干性、高增殖和免疫抑制的特点。MBNL1-AS1具有作为Basal型MIBC免疫响应生物标志物的潜能。
