RNA m⁶A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression

Abstract

Nitrogen 6-methyladenosine (m 6 A) is the result of methylation of nitrogen-6 on adenosine, and is the most abundant chemical modification of eukaryotic mRNA. Dysregulation of m 6 A methylation has been implicated in cancer development and progression through various mechanisms. This type of methylation is primarily regulated by methyltransferase-like 3 (METTL3). However, the molecular mechanisms underlying the role of METTL3 in colorectal cancer (CRC) have not been extensively elucidated. The present study explored m 6 A modification and the underlying mechanism of m 6 A, which serve regulatory roles in the development of CRC. It was found that METTL3 is upregulated in CRC cell lines and tissues, and its expression positively correlated with poor overall survival (OS). Mechanistically, the present study demonstrated that METTL3 methylates Snail mRNA, thus stabilizing it to promote CRC malignancy. The present findings indicate that m 6 A modification is involved in CRC tumorigenesis, and highlight its potential as a therapeutic target against CRC.

m6A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m6A-dependent manner

“…Increasing evidence has indicated that m 6 A key enzymes play critical role in human cancers, especially colorectal cancer. METTL3 is significantly upregulated in colorectal cancer tissues, and promotes its malignancy via stabilizing Snail mRNA [ 27 ]. In addition, METTL3 is reported to maintain SOX2 expression in an m 6 A-dependent mechanism to facilitate the progression of colorectal adenocarcinoma [ 28 ].…”

FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

“…The expression of SNAIL (Snail, SNAI1), a key transcription factor in EMT, has also been reported to be regulated by m6A in many diseases. In colorectal cancer, nasopharyngeal carcinoma, and hepatocellular carcinoma, METTL3 methylates Snail mRNA, thereby stabilising it and promoting tumour deterioration [ 52 , 53 , 54 ]. YTHDF1 mediates the translation of Snail mRNA with increased m6A in CDS, but not in the 3′ UTR, promoting cancer cell migration, invasion, and EMT in hepatocellular carcinoma [ 55 ].…”

METTL3 recruiting M2-type immunosuppressed macrophages by targeting m6A-SNAIL-CXCL2 axis to promote colorectal cancer pulmonary metastasis

“…Aberrant Snail expression is closely associated with EMT, which, in turn, is linked to the invasion, migration, metastasis, settlement, and growth capabilities of tumors, ultimately promoting the formation of CRPM [ 46 ]. In the field of colorectal cancer research, prior investigations have already elucidated the regulatory relationship between METTL3 and SNAIL [ 47 ]. However, these studies were limited to in vitro research, leaving unanswered the question of whether METTL3 continues to exert a similar influence in the context of colorectal cancer lung metastasis.…”