Liu Jie, Yao Lei, Chen Yating, Wang Xueyu, Wang Kun
Department of Head and Neck Thyroid Surgery, Cangzhou Hospital of Integrated TCM-WM Hebei, Canazhou, Hebei 061000, China.
Department of Head and Neck Thyroid Surgery, Cangzhou Hospital of Integrated TCM-WM Hebei, Canazhou, Hebei 061000, China.
Tissue Cell. 2025 Aug;95:102902. doi: 10.1016/j.tice.2025.102902. Epub 2025 Mar 31.
Downregulation of metallothionein 1 G (MT1G) has been demonstrated in papillary thyroid carcinoma (PTC) tissues. However, the underlying molecular mechanisms of MT1G in PTC progression need to be further explored.
MT1G and methyltransferase-like 3 (METTL3) mRNA levels were tested by quantitative real-time PCR. The protein levels of MT1G, METTL3, Wnt3A and β-catenin were measured by western blot. Cell proliferation, apoptosis, invasion and migration were measured by cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry, transwell assay and wound healing assay. MeRIP analysis was used to detect the MT1G methylation. The interaction between METTL3 and MT1G was evaluated using RIP assay and dual-luciferase reporter assay. A mouse xenograft model was also constructed to explore the roles of METTL3 and MT1G in vivo.
MT1G expression was downregulated in PTC, and its overexpression suppressed PTC cell growth, invasion and migration. METTL3-regulated m6A modification enhanced MT1G mRNA stability. Overexpression of METTL3 repressed PTC cell growth and metastasis, and this effect was reversed by MT1G knockdown. Besides, METTL3/MT1G axis could inhibit the activity of Wnt/β-catenin pathway. Meanwhile, METTL3 enhanced MT1G expression to suppress PTC tumor growth through Wnt/β-catenin pathway in vivo.
METTL3-mediated m6A modification of MT1G inhibited PTC cell growth and metastasis via inactivating the Wnt/β-catenin pathway.
在甲状腺乳头状癌（PTC）组织中已证实金属硫蛋白1G（MT1G）表达下调。然而，MT1G在PTC进展中的潜在分子机制仍需进一步探索。
通过定量实时PCR检测MT1G和甲基转移酶样3（METTL3）的mRNA水平。通过蛋白质印迹法检测MT1G、METTL3、Wnt3A和β-连环蛋白的蛋白水平。通过细胞计数试剂盒8检测、集落形成试验、EdU试验、流式细胞术、Transwell试验和伤口愈合试验检测细胞增殖、凋亡、侵袭和迁移。采用MeRIP分析检测MT1G甲基化。使用RIP试验和双荧光素酶报告基因试验评估METTL3与MT1G之间的相互作用。还构建了小鼠异种移植模型以探讨METTL3和MT1G在体内的作用。
MT1G在PTC中表达下调，其过表达抑制PTC细胞生长、侵袭和迁移。METTL3调节的m6A修饰增强了MT1G mRNA的稳定性。METTL3的过表达抑制了PTC细胞的生长和转移，而MT1G敲低可逆转这种作用。此外，METTL3/MT1G轴可抑制Wnt/β-连环蛋白通路的活性。同时，METTL3通过Wnt/β-连环蛋白通路增强MT1G表达以抑制体内PTC肿瘤生长。
METTL3介导的MT1G的m6A修饰通过使Wnt/β-连环蛋白通路失活来抑制PTC细胞生长和转移。
