METTL14 Suppresses Tumor Stemness and Metastasis of Colon Cancer Cells by Modulating m6A-Modified SCD1.

Abstract

Colon cancer (CC) is a malignant disease of the digestive tract, and its rising prevalence poses a grave threat to people's health. N6-methyladenosine (m6A) modification is essential for various crucial life processes through modulating gene expression. Methyltransferase-like 14 (METTL14), the m6A methylation transferase core protein, and its aberrant expression is intimately correlated to tumor development. This study was conducted to probe the impacts and specific mechanisms of METTL14 on the biological process of CC. Bioinformatics data disclosed that METTL14 was significantly attenuated in CC. Functional assays were executed to ascertain how METTL14 affected CC tumorigenicity, and METTL14 overexpression caused a notable decline in viability, migration, invasion, and stemness phenotype of CC cells. Then, in-depth mechanistic studies displayed that stearoyl-CoA desaturase 1 (SCD1) was a downstream target gene of METTL14-mediated m6A modification. METTL14 overexpression substantially augmented the m6A modification of SCD1 mRNA and diminished the SCD1 mRNA level. In addition, we revealed that YTHDF2 was the m6A reader to recognize METTL14 m6A-modified SCD1 mRNA and abolish its stability. Finally, we also validated that METTL14 might impede the tumorigenic process of CC through SCD1 mediated Wnt/β-catenin signaling. Taken together, this study presented that METTL14 performed as a potential therapeutic target in CC with important implications for the prognosis amelioration of CC patients.