METTL3-mediated m6A modification of CDCA7 mRNA promotes COAD progression

Colon adenocarcinoma (COAD) represents a frequent malignant tumor of the digestive system with high mortality and poor prognosis. As a prevalent internal mRNA modification in eukaryotic cells, N6-methyladenosine (m6A) has been reported to participate in tumor malignancy. This study is designed to explore the role and mechanism of Methyltransferase-like 3 (METTL3) in the progression of COAD.

In this research, the GEPIA database was applied to analyze the relationship between COAD and cell division cycle-associated protein 7 (CDCA7) or METTL3. Cell viability, cell cycle progression, apoptosis, migration, and invasion were detected by Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assays. The glycolysis level was detected via specific kits. CDCA7, E-cadherin, N-cadherin, and METTL3 protein levels were determined by western blot assay. The biological role of CDCA7 on COAD tumor growth was examined by the xenograft tumor model in vivo. After RBPsuite analysis, the interaction between METTL3 and CDCA7 was verified by methylated RNA immunoprecipitation (MeRIP).

METTL3 and CDCA7 were highly expressed in COAD tissues and cells. Furthermore, the silencing of CDCA7 hindered COAD cell proliferation, migration, invasion, glycolysis, EMT, and promoted apoptosis in vitro, as well as retarded tumor growth in vivo. At the molecular level, METTL3 might enhance the stability of CDCA7 mRNA via m6A methylation.

METTL3 contributes to the malignant progression of COAD cells partly by regulating the stability of CDCA7 mRNA, providing a promising therapeutic target for COAD treatment.