HNF4α-Mediated LINC02560 Promotes Papillary Thyroid Carcinoma Progression by Targeting the miR-505-5p/PDE4C Axis

• Published in: Biomolecules (Basel, Switzerland) Vol. 15; no. 5; p. 630
• Main Authors: Su, Yongcheng, Xu, Beibei, Gao, Chunyi, Pei, Wenbin, Ma, Miaomiao, Zhang, Wenqing, Hu, Tianhui, Zhang, Fuxing, Zhang, Shaoliang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.04.2025; MDPI
• Subjects: AKT protein; Binding sites; Cell culture; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Development and progression; Disease Progression; Enzymes; Epithelial-Mesenchymal Transition - genetics; Experiments; Female; Gene Expression Regulation, Neoplastic; Genetic aspects; growth and metastasis; Health aspects; Hepatocyte Nuclear Factor 4 - genetics; Hepatocyte Nuclear Factor 4 - metabolism; HNF4α; Humans; Laboratory animals; LINC02560; Male; Malignancy; Medical prognosis; Metabolism; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-505-5p; Papillary thyroid carcinoma; Pathogenesis; PDE4C; Phosphodiesterases; Physiological aspects; PTC; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Therapeutic targets; Thyroid cancer; Thyroid Cancer, Papillary - genetics; Thyroid Cancer, Papillary - metabolism; Thyroid Cancer, Papillary - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Transcription factors; Transfection; Variance analysis; Wound healing; China; New York; United States > US; Shanghai China; miR-505-5p; growth and metastasis; HNF4α; LINC02560; PTC; PDE4C
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom15050630

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid malignancy, and its progression is closely associated with patient outcomes. 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–mesenchymal transition (EMT) signaling pathways. Additionally, HNF4α was identified as a transcription factor capable of enhancing the expression of LINC02560. In conclusion, our findings elucidate the critical HNF4α/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.