TY  - EJOU
AU  - Guo, Xu 
AU  - Yu, Yanan 
AU  - Ma, Xiaolin 
AU  - Cai, Yuanjie 

TI  - Pan-Cancer Analysis of Enhancer-Induced PAN3-AS1 and Experimental Validation as a WFDC13-Promoting Factor in Colon Cancer
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 1
SN  - 1555-3906

AB  -  <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.
KW  - PAN3-AS1; pan-cancer; biomarker; immunotherapy; enhancer

DO  - 10.32604/or.2025.069274