Wu Hao, Xu Haochao, Jia Dongdong, Li Tao, Xia Liming
Department of Bone and Soft-Tissue Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Ann Transl Med. 2021 Jul;9(14):1155. doi: 10.21037/atm-21-2906.
Melanoma is a highly aggressive, malignant skin tumor with a statistically high mortality rate. N6-methyladenosine (mA) modification is involved in a variety of biological processes, including tumorigenesis. mA 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 mA 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 mA 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 mA-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.
黑色素瘤是一种侵袭性很强的恶性皮肤肿瘤，其死亡率在统计学上很高。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，如信使核糖核酸（mRNA）稳定性、核加工、转运、定位、翻译、初级微小核糖核酸（miRNA）加工以及RNA-蛋白质相互作用。几个成员（包括METTL3、METTL14、FTO、ALKBH5和YTHDF2）积极参与多种人类癌症。然而，尿苷胞苷激酶2（UCK2）参与黑色素瘤转移的基本机制尚未得到研究。UCK2在多种恶性肿瘤中上调。然而，UCK2在黑色素瘤中的复杂分子机制和治疗效果仍不清楚。
通过定量逆转录聚合酶链反应（qRT-PCR）评估UCK2的表达。基于功能缺失分析研究UCK2对PC细胞生物学特性的影响。进行免疫沉淀-定量聚合酶链反应（MeRIP-qPCR）以鉴定UCK2在黑色素瘤中的m6A靶向作用。
基于本研究的生物信息学分析，UCK2的上调可能在黑色素瘤中至关重要，并与不良生存相关。此外，由METTL3调节的m6A修饰导致黑色素瘤中UCK2信使核糖核酸（mRNA）稳定性增加。功能和机制实验表明，UCK2通过WNT/β-连环蛋白途径增强黑色素瘤癌细胞的转移。
在本研究中，我们发现m6A-METTL3轴诱导的异常UCK2表达通过增强Wnt/β-连环蛋白途径在黑色素瘤转移中起作用，这可能为黑色素瘤转移提供新线索。它也为黑色素瘤的预防和治疗提供了一个潜在靶点。
