Research Paper Volume 12, Issue 23 pp 23668—23683
DNMT3B silencing suppresses migration and invasion by epigenetically promoting miR-34a in bladder cancer
- 1 Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou, People’s Republic of China
- 2 Guangzhou Key Laboratory of Inflammatory and Immune Diseases, Zhujiang Hospital of Southern Medical University, Guangzhou, People’s Republic of China
- 3 School of Health Sciences, Macao Polytechnic Institute, Macao, People's Republic of China
Received: January 24, 2020 Accepted: June 29, 2020 Published: November 20, 2020
https://doi.org/10.18632/aging.103820How to Cite
Copyright: © 2020 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.