Promoter methylation is one of the most studied epigenetic modifications and it is highly relevant to the onset and progression of thyroid carcinoma (THCA). This study investigates the promoter methylation and expression pattern of intercellular adhesion molecule 5 (ICAM5) in THCA. CpG islands with aberrant methylation pattern in THCA, and the expression profiles of the corresponding genes in THCA, were analyzed using bioinformatics. ICAM5 was suggested to have a hypermethylation status, and it was highly expressed in THCA tissues and cells. Its overexpression promoted proliferation, mobility, and tumorigenic activity of THCA cells. As for the downstream signaling, ICAM5 was found to activate the MAPK/ERK and MAPK/JNK signaling pathways. Either inhibition of ERK or JNK blocked the oncogenic effects of ICAM5. DNA methyltransferases 1 (DNMT1) and DNMT3a were found to induce promoter hypermethylation of ICAM5 in THCA cells. Knockdown of DNMT1 or DNMT3a decreased the ICAM5 expression and suppressed malignant properties of THCA cells in vitro and in vivo, which were, however, restored by further artificial ICAM5 overexpression. Collectively, this study reveals that DNMT1 and DNMT3a mediates promoter hypermethylation and transcription activation of ICAM5 in THCA, which promotes malignant progression of THCA through the MAPK signaling pathway.

启动子甲基化是研究最多的表观遗传修饰之一，与甲状腺癌（THCA）的发病和进展高度相关。本研究探讨了 THCA 中细胞间粘附分子 5 (ICAM5) 的启动子甲基化和表达模式。利用生物信息学分析了THCA中甲基化模式异常的CpG岛以及THCA中相应基因的表达谱。ICAM5被认为具有高甲基化状态，并且在THCA组织和细胞中高表达。它的过度表达促进了 THCA 细胞的增殖、移动性和致瘤活性。至于下游信号传导，发现 ICAM5 激活 MAPK/ERK 和 MAPK/JNK 信号通路。抑制 ERK 或 JNK 均可阻断 ICAM5 的致癌作用。DNA 甲基转移酶 1 (DNMT1) 和 DNMT3a 被发现可诱导 THCA 细胞中 ICAM5 启动子高甲基化。敲低 DNMT1 或 DNMT3a 会降低 ICAM5 表达，并在体外和体内抑制 THCA 细胞的恶性特性，然而，进一步人工 ICAM5 过表达可以恢复这些特性。总的来说，本研究揭示DNMT1和DNMT3a介导THCA中ICAM5的启动子高甲基化和转录激活，从而通过MAPK信号通路促进THCA的恶性进展。