METTL1 facilitates colorectal cancer progression through internal m7G methylation of MACC1 and SDCCAG8 mRNA

N7-Methylguanosine (m7G) modification, as one of main types of RNA modification, has been implicated in several cancers. However, its function and regulatory mechanism in colorectal cancer (CRC) progression remain poorly understood. In this study, we found methyltransferase-like protein-1 (METTL1), the key m7G methyltransferase, is highly expressed in CRC tissues via whole-transcriptome sequencing, qRT-PCR and immunohistochemical analysis. Functional investigations revealed that METTL1 promotes CRC growth and proliferation both in vitro and in vivo, which depends on its m7G methyltransferase activity. Through m7G-MeRIP-sequencing and high-throughput mRNA sequencing, metastasis-associated in colon cancer 1 (MACC1) and serologically defined colon cancer antigen 8 (SDCCAG8) were identified as new targets of METTL1-mediated internal m7G modification. Further explorations confirmed that METTL1 regulates expression of the two genes by enhancing their mRNA stabilities. Overexpression of MACC1 or SDCCAG8 could rescue those phenotypic defects induced by METTL1 knockdown. Additionally, METTL1 expression is closely related to MACC1 or SDCCAG8 expression in CRC clinical samples. Collectively, these findings unveil that METTL1 facilitates CRC progression by regulating MACC1 and SDCCAG8 in an m7G-dependent manner, highlighting that METTL1 could be a potential therapeutic target in CRC.