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METTL14通过调节CALD1的mRNA和m6A水平促进口腔鳞状细胞癌进展。

METTL14 Promotes Oral Squamous Cell Carcinoma Progression by Regulating the mRNA and m6A Levels of CALD1.

作者信息

Chen Ruixue, Zhang Suxin, Li Hexiang, Yang Mengyuan, Lu Yiwen, Zhang Xudong

机构信息

Department of Endodontics, Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, 383# Zhong Shan East Road, Shijiazhuang, Hebei 50017, China.

Department of Oral and Maxillofacial, The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital, Hebei Medical University, 12#, JianKang Road, Shijiazhuang, Hebei 50017, China.

出版信息

J Environ Pathol Toxicol Oncol. 2023;42(3):71-81. doi: 10.1615/JEnvironPatholToxicolOncol.2022045134.

Abstract

Oral squamous cell carcinoma (OSCC) still threatens people's daily life. METTL14 is a newly discovered methyltransferase that catalyzes m6A methylation. Hence, this research was carried out to investigate the action mechanism of METTL14 in OSCC. The SCC-4 and UM2 cells, and tumorigenicity assay were utilized to investigate METTL14 roles in vitro and in vivo. Bioinformatic analysis was carried out with the UCSC, TCGA database and The Human Protein Atlas. The gene expression at mRNA and protein levels were measured by qRT-PCR and Western blot. In addition, cell growth and metastasis was analyzed by colony formation and transwell assays. MeRIP assay was performed to test the m6A levels of CALD1. The METTL14 and CALD1 levels were prominently expressed in OSCC cells. METTL14 silencing depleted the cell growth and metastasis. Furthermore, METTL14 silencing depleted the tumor growth in vivo. Additionally, the mRNA and m6A levels of CALD1 were depleted after METTL14 silencing. Overexpressed CALD1 neutralized the si-METTL14 effects in OSCC cells. In conclusion, METTL14 participated in the OSCC progression through modulating the mRNA and m6A levels of CALD1.

摘要

口腔鳞状细胞癌(OSCC)仍然威胁着人们的日常生活。METTL14是一种新发现的催化m6A甲基化的甲基转移酶。因此,本研究旨在探讨METTL14在OSCC中的作用机制。利用SCC-4和UM2细胞以及致瘤性试验来研究METTL14在体外和体内的作用。使用UCSC、TCGA数据库和人类蛋白质图谱进行生物信息学分析。通过qRT-PCR和蛋白质印迹法检测mRNA和蛋白质水平的基因表达。此外,通过集落形成和transwell试验分析细胞生长和转移情况。进行MeRIP试验以检测CALD1的m6A水平。METTL14和CALD1水平在OSCC细胞中显著表达。沉默METTL14可抑制细胞生长和转移。此外,沉默METTL14可抑制体内肿瘤生长。另外,沉默METTL14后,CALD1的mRNA和m6A水平降低。过表达CALD1可中和si-METTL14对OSCC细胞的影响。总之,METTL14通过调节CALD1的mRNA和m6A水平参与OSCC的进展。

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