淋巴转移是乳头状甲状腺癌（PTC）复发和进展的主要原因，其中长链非编码RNA（lncRNA）的失调被广泛证明与其有关。但是，在PTC中尚未确定与淋巴结转移相关的特定lncRNA。我们从癌症基因组图谱和临床样本中探索了PTC数据集中与淋巴结转移相关的lncRNA MFSD4A-AS1。在体外和体内调查了MFSD4A-AS1在淋巴转移中的作用。进行了生物信息学分析、荧光素酶检测和RNA免疫沉淀检测以确定MFSD4A-AS1在PTC淋巴转移中的潜在靶点和基本途径。MFSD4A-AS1在具有淋巴转移的PTC组织中特异性上调。上调MFSD4A-AS1促进了人脐静脉内皮细胞的网格形成和迁移，以及PTC细胞的浸润和迁移。重要的是，MFSD4A-AS1通过诱导淋巴生成和增强PTC细胞的浸润能力，在体内促进了PTC细胞的淋巴转移。进一步的机制解剖显示，MFSD4A-AS1作为竞争性内源性RNA，通过分散miR-30c-2-3p、miR-145-3p和miR-139-5p，破坏了miRNA介导的血管内皮生长因子A和C的抑制作用，并通过吸附miR-30c-2-3p进一步激活转化生长因子（TGF）β信号，该信号则靶向TGFBR2和USP15，两者协同促进了PTC的淋巴生成和淋巴转移。我们的研究揭示了MFSD4A-AS1促进PTC淋巴转移的新型双重机制，这将有利于开发PTC抗淋巴转移的治疗策略。

Lymphatic metastasis is the leading cause responsible for recurrence and progression in papillary thyroid cancer (PTC), where dysregulation of long non-coding RNAs (lncRNAs) has been extensively demonstrated to be implicated. However, the specific lymphatic node metastatsis-related lncRNAs remain not identified in PTC yet. Lymphatic node metastatsis-related lncRNA, MFSD4A-AS1, was explored in the PTC dataset from The Cancer Genome Atlas and our clinical samples. The roles of MFSD4A-AS1 in lymphatic metastasis were investigated in vitro and in vivo. Bioinformatic analysis, luciferase assay and RNA immunoprecipitation assay were performed to identify the potential targets and the underlying pathway of MFSD4A-AS1 in lymphatic metastasis of PTC. MFSD4A-AS1 was specifically upregulated in PTC tissues with lymphatic metastasis. Upregulating MFSD4A-AS1 promoted mesh formation and migration of human umbilical vein endothelial cells and invasion and migration of PTC cells. Importantly and consistently, MFSD4A-AS1 promoted lymphatic metastasis of PTC cells in vivo by inducing the lymphangiogenic formation and enhancing the invasive capability of PTC cells. Mechanistic dissection further revealed that MFSD4A-AS1 functioned as competing endogenous RNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of vascular endothelial growth factors A and C, and further activated transforming growth factor (TGF)-β signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC. Our results unravel novel dual mechanisms by which MFSD4A-AS1 promotes lymphatic metastasis of PTC, which will facilitate the development of anti-lymphatic metastatic therapeutic strategy in PTC.