Tissue & cell · 2025
METTL3-mediated m6A modification of MT1G inhibits papillary thyroid carcinoma cell growth and metastasis via Wnt/β-catenin pathway.
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Liu Jie, Yao Lei, Chen Yating, Wang Xueyu, Wang Kun
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: METTL3-mediated m6A modification of MT1G inhibited PTC cell growth and metastasis via inactivating the Wnt/β-catenin pathway.
METHODS: 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.
RESULTS: 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.
CONCLUSION: METTL3-mediated m6A modification of MT1G inhibited PTC cell growth and metastasis via inactivating the Wnt/β-catenin pathway.
Предметные рубрики MeSH
HumansMethyltransferasesWnt Signaling PathwayThyroid Cancer, PapillaryCell ProliferationAnimalsCell Line, TumorMetallothioneinCell MovementThyroid NeoplasmsMiceGene Expression Regulation, NeoplasticNeoplasm MetastasisMice, NudeApoptosisFemalebeta CateninAdenosineNeoplasm InvasivenessMice, Inbred BALB C