METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway.
METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway.
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DOI：
10.21037/atm-21-2906
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发表时间：
2021-07
影响因子：
--
通讯作者：
Xia L
中科院分区：
文献类型：
--
作者：
Wu H;Xu H;Jia D;Li T;Xia L
黑色素瘤是一种高度侵袭性的恶性皮肤肿瘤，具有统计学上的高死亡率。N6-甲基腺苷（m6A）修饰参与多种生物学过程，包括肿瘤发生。m6A修饰调节RNA的命运和功能，例如mRNA稳定性、核加工、转运、定位、翻译、初级microRNA（miRNA）加工和RNA-蛋白质相互作用。几个成员（包括胃L3、胃L14、FTO、ALKBH 5和YTHDF 2）积极参与多种人类癌症。然而，尿苷胞苷激酶2（UCK 2）参与黑色素瘤转移的基本机制尚未研究。UCK2在多种恶性肿瘤中上调。然而，UCK 2在黑色素瘤中的复杂分子机制和治疗作用仍不清楚。通过qRT-PCR评估UCK 2的表达。在功能丧失分析的基础上研究了UCK 2对PC细胞生物学特性的影响。进行免疫沉淀-qPCR（MeRIP-qPCR）以鉴定UCK 2在黑素瘤癌中的m6A靶向作用。基于本研究中的生物信息学分析，UCK 2的上调可能在黑色素瘤中是必需的，并且与较差的生存率相关。此外，在黑色素瘤癌中，由胃L3调节的m6A修饰导致UCK 2增加信使RNA（mRNA）的稳定性。功能和机制实验表明，UCK 2通过WNT/β-catenin途径增强黑色素瘤癌细胞的转移。本研究发现m6A-L3轴诱导的UCK 2异常表达通过增强Wnt/β-catenin通路在黑色素瘤转移中发挥作用，这可能为黑色素瘤转移提供新的线索。它也为黑色素瘤的预防和治疗提供了一个潜在的靶点。
Melanoma is a highly aggressive, malignant skin tumor with a statistically high mortality rate. N6-methyladenosine (m6A) modification is involved in a variety of biological processes, including tumorigenesis. m6A modifications regulate the fate and functions of RNA, such as mRNA stability, nuclear processing, transport, localization, translation, primary microRNA (miRNA) processing, and RNA-protein interactions. Several members (including METTL3, METTL14, FTO, ALKBH5, and YTHDF2) are actively involved in a variety of human cancers. However, the basic mechanism of the involvement of uridine cytidine kinase 2 (UCK2) in melanoma metastasis has not been studied. UCK2 is upregulated in a variety of malignancies. However, the complex molecular mechanisms and therapeutic effects of UCK2 in melanoma remain unclear. The expression of UCK2 was evaluated by qRT-PCR. The effects of UCK2 on the biological characteristics of PC cells were investigated on the basis of loss-of-function analyses. Immunoprecipitation-qPCR (MeRIP-qPCR) was performed to identify the m6A targeted effect of UCK2 in melanoma cancer. Based on the bioinformatics analysis in this study, up-regulation of UCK2 could be essential in melanoma cancer, and associated with poor survival. Furthermore, the m6A modification regulated by METTL3 led to UCK2 increased messenger RNA (mRNA) stability in melanoma cancer. Functional and mechanistic experiments indicated that UCK2 enhanced the metastasis of melanoma cancer cells through the WNT/β-catenin pathway. In this study, we found that m6A-METTL3 axis induced abnormal UCK2 expression plays a role in melanoma metastasis by enhancing the Wnt/β-catenin pathway, which may provide new clues for melanoma metastasis. It also provides a potential target for the prevention and treatment of melanoma.
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影响因子：
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影响因子：
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