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This study investigated the role of the long non-coding RNA LINC02560 in the pathogenesis and aggressiveness of PTC through cell culture, transfection, RT-qPCR, Western blot analysis, and various functional assays, such as MTT, EdU, colony formation, wound healing, and Transwell migration assays. Our results revealed a significant upregulation of LINC02560 in PTC tissues, correlating with poor prognosis in affected patients. Functional analyses demonstrated that silencing of LINC02560 markedly inhibited the proliferation, migration, and invasion of the PTC cell lines, KTC-1, and BCPAP, whereas overexpression promoted these aggressive traits. Mechanistically, LINC02560 acted as a competitive endogenous RNA, sponging miR-505-5p and alleviating its suppression on PDE4C degradation, thereby activating the P-AKT and epithelial\u2013mesenchymal transition (EMT) signaling pathways. Additionally, HNF4\u03b1 was identified as a transcription factor capable of enhancing the expression of LINC02560. In conclusion, our findings elucidate the critical HNF4\u03b1\/LINC02560\/miR-505-5p\/PDE4C axis in PTC pathology, presenting this regulatory network as a promising biomarker combination and potential therapeutic target to improve patient outcomes and survival rates, warranting further clinical investigation to validate these insights and support the development of targeted therapies in PTC management.<\/jats:p>","DOI":"10.3390\/biom15050630","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:28:11Z","timestamp":1746174491000},"page":"630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["HNF4\u03b1-Mediated LINC02560 Promotes Papillary Thyroid Carcinoma Progression by Targeting the miR-505-5p\/PDE4C Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Yongcheng","family":"Su","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"},{"name":"Department of Breast Surgery, The First Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-5145","authenticated-orcid":false,"given":"Tianhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"},{"name":"Department of General Surgery, The First Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China"},{"name":"Shenzhen Research Institute of Xiamen University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine and Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.7150\/thno.66142","article-title":"KDM1A promotes thyroid cancer progression and maintains stemness through the Wnt\/\u03b2-catenin signaling pathway","volume":"12","author":"Zhang","year":"2022","journal-title":"Theranostics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/s13046-019-1321-x","article-title":"Hsa_circ_0058124 promotes papillary thyroid cancer tumorigenesis and invasiveness through the NOTCH3\/GATAD2A axis","volume":"38","author":"Yao","year":"2019","journal-title":"J. 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