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ARTICLE

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

Xu Guo1, Yanan Yu2, Xiaolin Ma3, Yuanjie Cai1,*
1 Department of Breast Surgery, Zhejiang Hospital, Hangzhou, 310013, China
2 Clinical Research Center, Affiliated Hospital of Shandong Second Medical University, Weifang, 261041, China
3 Department of Oncology, Affiliated Hospital of Shandong Second Medical University, Weifang, 261041, China
* Corresponding Author: Yuanjie Cai. Email: email
(This article belongs to the Special Issue: Long Non-coding RNAs (lncRNAs) and Cancer: A Focus on Four Key Areas)

Oncology Research https://doi.org/10.32604/or.2025.069274

Received 19 June 2025; Accepted 13 October 2025; Published online 14 November 2025

Abstract

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.

Keywords

PAN3-AS1; pan-cancer; biomarker; immunotherapy; enhancer

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