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.
