文章：

METTL3介导的n6 -甲基腺苷修饰DUSP5 mRNA促进胆囊癌进展

METTL3-mediated N6-methyladenosine modification of DUSP5 mRNA promotes gallbladder-cancer progression 

原文发布日期：2021-11-19 

英文摘要：

N6-methyladenosine (m6A) RNA methylation and its associated methyltransferase METTL3 play an important role in tumorigenesis of a series of tumors. However, dysregulation of METTL3 in gallbladder cancer (GBC) remains obscure. Here, we showed that upregulated METTL3 level predicted poor prognosis and correlated with increased lymphatic metastasis and high TNM stage. Functionally, we found that METTL3 could promote cell proliferation, invasion, and migration of GBC-SD and NOZ cells. Mechanistically, we revealed the METTL3-mediated m6A-modification profile in GBC cells and identified DUSP5 as the downstream gene of METTL3. METTL3 promoted the degradation of DUSP5 mRNA in a YTHDF2-dependent manner. Rescue assays showed that downregulation of DUSP5 could attenuate the knockdown METTL3-mediated inhibition of cell proliferation, invasion, and migration of GBC-SD and NOZ cells. Thus, our finding shows that elevated METTL3 expression contributes to tumor aggression in GBC, suggesting that METTL3 is a possible prognostic predictor and therapeutic target against GBC. 

摘要翻译： 

N6-甲基腺苷（m6A）RNA甲基化及其相关甲基转移酶METTL3在多种肿瘤的发生发展中起重要作用，但METTL3在胆囊癌（GBC）中的调控机制尚不明确。本研究显示，METTL3表达上调预示不良预后，并与淋巴结转移增多和高TNM分期相关。功能实验表明，METTL3可促进GBC-SD和NOZ细胞的增殖、侵袭和迁移。机制研究发现，METTL3通过介导GBC细胞中m6A修饰模式，并确定DUSP5作为其下游靶基因。METTL3以YTHDF2依赖性方式促进DUSP5 mRNA的降解。挽救实验证实，下调DUSP5可逆转METTL3敲低对GBC-SD和NOZ细胞增殖、侵袭和迁移的抑制作用。综上，METTL3表达升高促进胆囊癌的侵袭性进展，表明METTL3可能作为胆囊癌的预后预测指标和治疗靶点。

原文链接：

METTL3-mediated N6-methyladenosine modification of DUSP5 mRNA promotes gallbladder-cancer progression