甲状腺乳头状癌（PTC）是全世界最常见的甲状腺恶性肿瘤类型。致癌转录因子 (TF) 驱动转录重编程和肿瘤发生。 myc 相关锌指蛋白 (MAZ) 是 Myc 家族 TF 之一。 MAZ 在 PTC 发病机制中的作用仍然很大程度上未知。在此，我们报告 MAZ 通过激活 MAPK 信号传导，在体外和体内深刻促进 PTC 细胞的增殖。我们首先分析了 MAZ 沉默后 PTC 细胞的基因表达。 BRAF、KRAS和LOC547被确定为TF MAZ的重要靶基因。特别是，TF MAZ 与 BRAF 或 KRAS 的启动子结合，显着提高了它们的转录和表达水平。同时，MAZ 可以显着提高 LOC547 作为 TF 的转录和表达。高水平的LOC547将ACTN4蛋白从细胞核转移到细胞质，改善细胞质中ACTN4和EGFR之间的蛋白质-蛋白质相互作用，增强ERK1/2磷酸化，激活MAPK信号传导，从而促进PTC进展。我们的数据确定了以前未被充分认识的 MAZ 控制的转录重编程和通过 BRAF、KRAS 和 LOC547 激活的 ERK1/2。我们的数据表明 MAZ 控制轴的激活促进甲状腺肿瘤的发生。这些见解将增进我们对 TF 在癌症发展中的作用的了解，并强调 TF 作为未来癌症治疗靶点的潜力。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancies worldwide. Oncogenic transcription factors (TFs) drive transcriptional reprogramming and tumorigenesis. The myc-associated zinc finger protein (MAZ) is one of the Myc family TFs. The role of MAZ in PTC pathogenesis is still largely unknown. Here, we report that MAZ profoundly promotes proliferation of PTC cells ex vivo and in vivo through activating MAPK signaling. We firstly profiled gene expression of PTC cells after silencing of MAZ. BRAF, KRAS and LOC547 were identified as important target genes of TF MAZ. In particular, TF MAZ bound to the promoters of BRAF or KRAS and significantly increased their transcription and expression levels. Meanwhile, MAZ could noticeably elevate LOC547 transcription and expression as a TF. High levels of LOC547 relocated ACTN4 protein from the nucleus to the cytosol, improved protein-protein interactions between ACTN4 and EGFR in the cytosol, enhanced ERK1/2 phosphorylation, activated the MAPK signaling and, thus, promoted PTC progression. Our data identify a previously underappreciated MAZ-controlled transcriptional reprogram and ERK1/2 activation via BRAF, KRAS and LOC547. Our data illustrate that activation of the MAZ-controlled axis promotes thyroid tumorigenesis. These insights would advance our knowledge of the role of TFs in cancer development and highlight the potential of TFs as future targets for treatments against cancers.Copyright © 2024 Elsevier B.V. All rights reserved.