METTL14 通过调节 N6-甲基腺苷依赖的初级 microRNA 加工来抑制肝癌的转移潜力。

METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N -methyladenosine-dependent primary MicroRNA processing.

机构信息

Department of Medical Genetics, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

出版信息

Hepatology. 2017 Feb;65(2):529-543. doi: 10.1002/hep.28885. Epub 2016 Dec 24.

DOI:10.1002/hep.28885

PMID:27774652

Abstract

UNLABELLED

N -Methyladenosine (m A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m A modifications are decreased in hepatocellular carcinoma, especially in metastatic hepatocellular carcinoma, and that methyltransferase-like 14 (METTL14) is the main factor involved in aberrant m A modification. Moreover, METTL14 down-regulation acts as an adverse prognosis factor for recurrence-free survival of hepatocellular carcinoma and is significantly associated with tumor metastasis in vitro and in vivo. We confirm that METTL14 interacts with the microprocessor protein DGCR8 and positively modulates the primary microRNA 126 process in an m A-dependent manner. Further experiments show that microRNA 126 inhibits the repressing effect of METTL14 in tumor metastasis.

CONCLUSION

These studies reveal an important role of METTL14 in tumor metastasis and provide a fresh view on m A modification in tumor progression. (Hepatology 2017;65:529-543).

摘要

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N-甲基腺苷（m A）修饰参与了许多生物学过程。然而，其在癌症中的作用尚未得到很好的研究。在这里，我们证明 m A 修饰在肝细胞癌中减少，特别是在转移性肝细胞癌中，并且甲基转移酶样 14（METTL14）是涉及异常 m A 修饰的主要因素。此外，METTL14 的下调可作为肝细胞癌无复发生存的不利预后因素，并且与体外和体内肿瘤转移显著相关。我们证实 METTL14 与微处理器蛋白 DGCR8 相互作用，并以 m A 依赖性方式正向调节初级 microRNA 126 过程。进一步的实验表明 microRNA 126 抑制了 METTL14 在肿瘤转移中的抑制作用。