METTL14通过调节AOC1 mRNA的稳定性促进鼻咽癌的进展。
METTL14 contributes to the progression of nasopharyngeal carcinoma through regulating the stability of AOC1 mRNA.
发表日期:2024 Jul 02
作者:
Changan Hu, Shengguan Song, Shanglong Zhao, Zhen Xue, Xiwen Zhu
来源:
Cell Death & Disease
摘要:
鼻咽癌(NPC)是鼻咽粘膜的恶性上皮性肿瘤,在世界范围内发病率较高。甲基转移酶样 14 (METTL14) 是一种主要的 RNA N6-腺苷甲基转移酶,通过调节 RNA 功能参与肿瘤进展。 本研究旨在探讨METTL14在鼻咽癌中的生物学功能和机制。采用实时定量聚合酶链式反应(RT-qPCR)检测METTL14和含铜胺氧化酶1(AOC1)的表达。使用蛋白质印迹法测量 METTL14、AOC1、Cyclin D1、B 细胞淋巴瘤-2 (Bcl-2) 和 N-钙粘蛋白的蛋白水平。使用 5-乙炔基-2'-脱氧尿苷 (EdU)、集落形成、流式细胞术、伤口划痕和 Transwell 测定来评估细胞增殖、周期进展、凋亡、迁移和侵袭。 METTL14 和 AOC1 之间的相互作用通过 RNA 免疫沉淀 (RIP)、甲基化 RNA 免疫沉淀 (MeRIP) 和双荧光素酶报告基因测定进行验证。通过体内异种移植肿瘤模型研究了METTL14对鼻咽癌肿瘤生长的生物学作用。METTL14和AOC1在鼻咽癌组织和细胞中高表达。此外,METTL14敲低可能会阻断NPC细胞的增殖、迁移、侵袭,并在体外诱导细胞凋亡。在机制上,METTL14可能通过m6A甲基化增强AOC1 mRNA的稳定性。 METTL14 沉默可能会抑制体内鼻咽癌肿瘤的生长。METTL14 可能部分通过调节 AOC1 mRNA 的稳定性来促进鼻咽癌细胞的发育,这为鼻咽癌治疗提供了一个有前景的治疗靶点。© 2024。作者。
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor of the nasopharyngeal mucosa with a high incidence rate all over the world. Methyltransferase-like 14 (METTL14) is a major RNA N6-adenosine methyltransferase implicated in tumor progression by regulating RNA function. This study is designed to explore the biological function and mechanism of METTL14 in NPC.METTL14 and Amine oxidase copper containing 1 (AOC1) expression were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of METTL14, AOC1, Cyclin D1, B-cell lymphoma-2 (Bcl-2), and N-cadherin were measured using western blot. Cell proliferation, cycle progression, apoptosis, migration, and invasion were assessed using 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, flow cytometry, wound scratch, and transwell assays. The interaction between METTL14 and AOC1 was verified using RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), and dual-luciferase reporter assays. The biological role of METTL14 on NPC tumor growth was examined by the xenograft tumor model in vivo.METTL14 and AOC1 were highly expressed in NPC tissues and cells. Moreover, METTL14 knockdown might block NPC cell proliferation, migration, invasion, and induce cell apoptosis in vitro. In mechanism, METTL14 might enhance the stability of AOC1 mRNA via m6A methylation. METTL14 silencing might repress NPC tumor growth in vivo.METTL14 might boosted the development of NPC cells partly by regulating the stability of AOC1 mRNA, which provided a promising therapeutic target for NPC treatment.© 2024. The Author(s).