Abstract
The role of DNA methyltransferase 3B (DNMT3B) in tumorigenesis and development has been widely recognized; however, the mechanism underlying its action remains unclear. Considering its function in de novo methylation, we aimed to investigate whether DNMT3B plays its role via microRNA (miR)-34a promoter methylation in bladder cancer. We found that DNMT3B expression was low in 10 bladder cancer tissues and high in 20 bladder cancer tissues. miR-34a expression was higher in bladder cancer tissues with low expression of DNMT3B than that in bladder cancer tissues with high expression of DNMT3B. The level of miR-34a was negatively correlated with the level of DNMT3B. The methylation ratio of the miR-34a promoter was positively correlated with the level of DNMT3B and negatively correlated with the level of miR-34a. DNMT3B knockdown increased the expression of miR-34a and the transcriptional activity of the miR-34a promoter, while decreasing miR-34a promoter methylation. DNMT3B knockdown inhibited migration and invasion, while decreasing the protein levels of hepatocyte nuclear factor 4 gamma and Notch1 which are downstream targets of miR-34a. These inhibitory effects of DNMT3B were mitigated by the miR-34a inhibitor. In conclusion, DNMT3B silencing suppresses migration and invasion by epigenetically promoting miR-34a in bladder cancer.
Highlights
Bladder cancer, a malignant tumor in the bladder mucosa, is the 10th most common type of cancer worldwide [1]
Due to its function in de novo methylation, we hypothesized that DNA methyltransferase 3B (DNMT3B) might be a key factor that stimulates promoter methylation of the genes involved in bladder cancer progression and metastasis
We investigated the clinical significance of DNMT3B expression and the underlying mechanisms of DNMT3B in promoting the migration and invasion of bladder cancer
Summary
A malignant tumor in the bladder mucosa, is the 10th most common type of cancer worldwide [1]. DNMT3B is upregulated in various malignant tumors, such as lung cancer, hepatocellular carcinoma, prostate cancer, melanoma, and bladder cancer. It is www.aging-us.com widely recognized to be involved in the regulation of tumor initiation and progression [3,4,5,6,7,8,9], but the mechanism remains unclear. Due to its function in de novo methylation, we hypothesized that DNMT3B might be a key factor that stimulates promoter methylation of the genes involved in bladder cancer progression and metastasis
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