DNMT3b affects colorectal cancer development by regulating FLI1 through DNA hypermethylation

• Published in: The Kaohsiung journal of medical sciences Vol. 39; no. 4; pp. 364 - 376
• Main Authors: Zhou, Lei, Pan, Li‐Zhen, Fan, Yue‐Juan
• Format: Journal Article
• Language: English
• Published: BP, Asia Wiley Publishing Asia Pty Ltd 01.04.2023; John Wiley & Sons, Inc; Wiley
• Subjects: Analysis; Antibodies; Apoptosis; Bioinformatics; Biotechnology industry; Cancer; Cell Proliferation - genetics; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA methylation; DNA Methylation - genetics; DNMT3b; Epigenetics; Ethylenediaminetetraacetic acid; Ewings sarcoma; FLI1; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Humans; Leukemia; Medical prognosis; Methylation; Methyltransferases; MicroRNAs; Phenotype; Proto-Oncogene Protein c-fli-1 - metabolism; Scientific equipment and supplies industry; Survival analysis; United States; China; United Kingdom > UK; Germany; DNA methylation; DNMT3b; colorectal cancer; FLI1; epigenetics
• ISSN: 1607-551X; 2410-8650
• DOI: 10.1002/kjm2.12647

Friend leukemia integration 1 (FLI1) is an ETS transcription factor family member. Here, we identified cg11017065 as the most hyper‐methylated cytosine and guanine (CpG) in colorectal cancer (CRC), which belongs to the FLI1 gene. Moreover, integrated bioinformatics prediction and analysis of our cohort showed that FLI1 expression was downregulated and DNA methylation was elevated in CRC. Bioinformatics prediction also indicated that patients overexpressing FLI1 had higher survival rates than those with low FLI1 expression. CRC cells with ectopic expression of FLI1 had reduced invasion, migration, cloning ability and increased apoptosis. Furthermore, DNA‐methyltransferase 3b (DNMT3b) was found to be significantly overexpressed in CRC, and low DNMT3b expression predicted a prolonged survival. DNMT3b bound to the FLI1 promoter. Inhibition of DNMT3b increased FLI1 expression and inhibited the malignant phenotype of CRC cells. Inhibition of FLI1 reversed the phenotypic modulation by DNMT3b depletion in vitro and in vivo. In conclusion, our data indicate that DNMT3b potentiates CRC cell proliferation, migration, and invasion through downregulating FLI1.