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Qiu-Yu Lin,1,* Qian-Le Qi,1,* Sen Hou,1 Zhen Chen,2 Laney Zhang,3 Hong-Guang Zhao,1 Cheng-He Lin1 1Nuclear Medicine Department, The First Hospital of Jilin University, Changchun City 130000, Jilin Province, People’s Republic of China; 2Chengdu Xinke Pharmaceutical Co., LTD, Chengdu City 610000, Sichuan Province, People’s Republic of China; 3Biological Sciences at Cornell University (2022), Ithaca, NY, USA*These authors contributed equally to this workCorrespondence: Cheng-He LinNuclear Medicine Department, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun City 130000, Jilin Province, People’s Republic of ChinaTel +86 431-88782766Email linchenghejl@163.comIntroduction: Thyroid cancer (TC) is an endocrine tumor whose risk of onset has been rising, so the deep understanding of its molecular mechanism helps formulate new treatment strategies.Methods: This paper was aimed at exploring the regulatory mechanism of long non-coding RNA (LncRNA) plasmacytoma variant translocation 1 (PVT1) in TC. The expression of PVT1, miR-423-5p and p21-activated kinase 3 (PAK3) in TC tissues and cell lines was detected by real-time PCR. PAK3 levels were detected by Western blot. Regulatory relationships between target genes and the proliferation, invasion and apoptosis of cells and genes were analyzed.Results: PVT1 and PAK3 upregulated while miR-423-5p downregulated in the tissues and cell lines. PVT1 downregulation inhibited TC cells from malignantly proliferating and invading, and promoted their apoptosis. PVT1 specifically regulated miR-423-5p, and its overexpression could weaken the anti-tumor effect of this miR on TC cells. In addition, miR-423-5p directly targeted PAK3, and knocking down its expression could weaken the inhibitory effect of PAK3 downregulation on TC progression. Besides, PVT1 acted as a competitive endogenous RNA to sponge this miR and thus regulate PAK3 expression.Discussion: In conclusion, PVT1 can mediate the molecular mechanism of the miR-423-5p-PAK3 axis regulatory network on regulating TC, so it is a new direction of treating the disease.Keywords: PVT1, thyroid cancer, miR-423-5p, PAK3