@Article{or.2025.069274,
AUTHOR = {Xu Guo, Yanan Yu, Xiaolin Ma, Yuanjie Cai},
TITLE = {Pan-Cancer Analysis of Enhancer-Induced PAN3-AS1 and Experimental Validation as a WFDC13-Promoting Factor in Colon Cancer},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {1},
PAGES = {0--0},
URL = {http://www.techscience.com/or/v34n1/65177},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <i>In vitro</i> 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. <b>Conclusion:</b> 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.},
DOI = {10.32604/or.2025.069274}
}