Methyltransferase-like factor 3 is highly expressed and promotes the malignant phenotype of colon cancer
XIANG Yilan1, HU Yuanbo2, HUANG Tingting3, CHEN Xietao2, CHEN Chenbin2, LU Mingdong2
1.Department of Radiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China;2.Department of Gastrointestinal Surgery, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; 3.Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou 325035, China
XIANG Yilan,HU Yuanbo,HUANG Tingting, et al. Methyltransferase-like factor 3 is highly expressed and promotes the malignant phenotype of colon cancer[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(11): 889-895，904.
Abstract：Objective: To evaluate the expression characteristics and clinical prognostic relevance of methyltransferase-like factor 3 (METTL3) in colon cancer patients, and to investigate the effect of METTL3 expression on different biological phenotypes of colon cancer cells. Methods: Comprehensive analysis of the expression differences of METTL3 gene in 1278 colon cancer tissues and 41 adjacent tissues from the TCGA database and 4 different GEO datasets. Kaplan-Meier curve was used to analyze the impact of METTL3 expression on the prognosis of colon cancer patients. A total of 481 colon cancer tissues and 59 paracancerous tissues from patients admitted to the First Affiliated Hospital of Wenzhou Medical University who underwent radical surgery between 2014 and 2018 were collected, retrospectively. Immunohistochemistry was used to determine the expression of METTL3. Small interfering RNA (siRNA) was used to knockdown the expression levels of METTL3in colon cancer cell lines DLD-1 and HCT-116. The biological function of METTL3 in colon cancer cells was evaluated by CCK-8 and Transwell assays. Results: In colon cancer tissue samples from the TCGA database and our cohort, METTL3 had significantly up-regulated expression in colon cancer tissue than that in adjacent tissues (P<0.001). The results of survival analysis showed that higher expression of METTL3 was associated with shorter overall survival (Log-rank P=0.028) and disease-free survival (Log-rank P=0.035) in colon cancer patients.Univariate and multivariate Cox analysis results showed that METTL3 could serve as an independent risk factorfor the prognosis of colon cancer patients (HR=1.335, 95%CI=1.032-1.738, P=0.030). Meanwhile, METTL3 knock-down could significantly inhibit the proliferation (P<0.01), migration, and invasion ability (P<0.01) of colon cancer cells. Conclusion: METTL3 is upregulated in colon cancer tissue and could serve as an independent factor for poor prognosis in colon cancer patients. Knocking down the expression of METTL3 could inhibit the malignant phenotype of colon cancer cells. METTL3 may be involved as a carcinogenic gene in the malignant progression of colon cancer.
