Cancer Gene Therapy ( IF 6.4 ) Pub Date : 2024-01-24 , DOI: 10.1038/s41417-024-00731-5 Rui Yang , Cheng Yang , Danjie Su , Yang Song , Jie Min , Zhixin Qian , Xiangjing Shen , Junqiang Li , Haichuan Su
Ran GTPase activating protein 1 (RanGAP1) has been implicated in various diseases, but its role in colorectal cancer (CRC) progression remains unclear. Using tumor tissues and public databases, we found that RanGAP1 was significantly upregulated in CRC tissues and was associated with poor prognosis of patients. N6-methyladenosine (m6A) was found to play an important role in higher expression of RanGAP1. MeRIP-seq, RIP-qPCR, Luciferase reporter assays and other related experiment elucidated the molecular mechanism underlying m6A modification of RanGAP1. Besides, cell function experiments and xenograft tumor models corroborated the function of RanGAP1 in CRC progression. By RNA-seq and related analysis, RanGAP1 was verified to influent CRC progression via the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Therefore, N6-methyladenosine modification of RanGAP1 by METTL3/YTHDF1 plays a role in CRC progression through the MAPK pathway and could be a potential biomarker and therapeutic target for CRC.
中文翻译:
METTL3介导的RanGAP1通过招募YTHDF1通过MAPK途径促进结直肠癌进展
Ran GTP 酶激活蛋白 1 (RanGAP1) 与多种疾病有关,但其在结直肠癌 (CRC) 进展中的作用仍不清楚。使用肿瘤组织和公共数据库,我们发现 RanGAP1 在 CRC 组织中显着上调,并且与患者不良预后相关。研究发现 N6-甲基腺苷 (m6A) 在 RanGAP1 的较高表达中发挥重要作用。MeRIP-seq、RIP-qPCR、荧光素酶报告基因检测等相关实验阐明了m6A修饰RanGAP1的分子机制。此外,细胞功能实验和异种移植肿瘤模型证实了RanGAP1在CRC进展中的功能。通过 RNA-seq 和相关分析,证实 RanGAP1 通过丝裂原激活蛋白激酶 (MAPK) 信号通路影响 CRC 进展。因此,METTL3/YTHDF1 对 RanGAP1 的 N6-甲基腺苷修饰通过 MAPK 途径在 CRC 进展中发挥作用,并可能成为 CRC 的潜在生物标志物和治疗靶点。