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Abstract：
N6-methyladenosine (m6A) methylation mediates cancer development by regulating cell proliferation and metastasis. This study aimed to identify whether methyltransferase 14 (METTL14) affects gastric cancer (GC) cellular functions and its underlying mechanism. METTL14 and TATA-box binding protein associated factor 10 (TAF10) levels were examined using quantitative real-time PCR, immunohistochemical assay, and Western blot. Biological functions were assessed using cell counting kit-8, colony formation, and transwell assays. The interaction between METTL14 and TAF10 was analyzed using RNA immunoprecipitation, methylated RNA immunoprecipitation, and luciferase reporter assay. A xenograft tumor mouse model was established to assess the role of METTL14 in vivo. The results suggested that METTL14 was low expressed and TAF10 was highly expressed in GC tissues and cells. METTL14 overexpression inhibited GC cell viability, colony, migration, and invasion. TAF10 was predicted and confirmed to be negatively related to METTL14. METTL14 promoted m6A methylation of TAF10 and inhibited TAF10 stability. Moreover, TAF10 counteracted the cellular behaviors regulated by METTL14. Overexpression of METTL14 inhibited tumor growth and histopathology. In conclusion, METTL14 inhibits GC progression by attenuating GC cell proliferation, migration, and invasion. Mechanistically, METTL14 promoted m6A methylation of TAF10, suppressed the stability of TAF10, and thus downregulated the TAF10 levels, These results provide a new insight into GC therapy.
摘要：
N6-甲基腺苷(m6A)甲基化通过调节细胞增殖和转移介导癌症发展。本研究旨在确定甲基转移酶14（METTL14）是否影响胃癌（GC）细胞功能及其潜在机制。使用定量实时PCR检测METTL14和TATA-box结合蛋白相关因子10(TAF10)水平,免疫组织化学测定，和Westernblot。使用细胞计数试剂盒-8评估生物学功能，集落形成，和transwell分析。使用RNA免疫沉淀分析了METTL14和TAF10之间的相互作用，甲基化RNA免疫沉淀，和荧光素酶报告基因测定。建立异种移植肿瘤小鼠模型以评估METTL14在体内的作用。结果表明，在GC组织和细胞中，METTL14低表达，TAF10高表达。METTL14过表达抑制GC细胞活力，殖民地,迁移,和入侵。TAF10被预测并证实与METTL14呈负相关。METTL14促进TAF10的m6A甲基化并抑制TAF10稳定性。此外，TAF10抵消了METTL14调节的细胞行为。METTL14的过表达抑制肿瘤生长和组织病理学。总之,METTL14通过减弱GC细胞增殖来抑制GC进展，迁移,和入侵。机械上,METTL14促进TAF10的m6A甲基化，抑制TAF10的稳定性，从而下调TAF10水平，这些结果为GC治疗提供了新的见解。
