METTL3 通过 m6A 依赖方式稳定 PLAU mRNA 促进结直肠癌转移。

METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner.

机构信息

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Biochem Biophys Res Commun. 2022 Jul 23;614:9-16. doi: 10.1016/j.bbrc.2022.04.141. Epub 2022 May 6.

DOI:10.1016/j.bbrc.2022.04.141

PMID:35567945

Abstract

Colorectal cancer (CRC) is one of the most common tumors and ranks second in tumor mortality. N6-methyladenosine (m6A) modification is the most prevalent RNA modification in eukaryotes. As the critical m6A methyltransferase, the role of METTL3 in the metastasis regulation of CRC might be controversial and need to be further explored. In this study, we confirmed that METTL3 could promoted CRC metastasis in vitro and in vivo. METTL3 was upregulated in CRC tissues and led to poor survival in CRC metastasis. We found METTL3 upregulated PLAU mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC. Our study provided new therapeutic targets in CRC metastasis treatment.

摘要

结直肠癌（CRC）是最常见的肿瘤之一，在肿瘤死亡率中排名第二。N6-甲基腺苷（m6A）修饰是真核生物中最普遍的 RNA 修饰。作为关键的 m6A 甲基转移酶，METTL3 在 CRC 转移调控中的作用可能存在争议，需要进一步探索。在这项研究中，我们证实 METTL3 可以促进 CRC 的体外和体内转移。METTL3 在 CRC 组织中上调，并导致 CRC 转移中的不良生存。我们发现 METTL3 以 m6A 依赖的方式上调 PLAU mRNA，然后参与 MAPK/ERK 途径促进 CRC 血管生成和转移。我们的研究为 CRC 转移治疗提供了新的治疗靶点。