DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy

Abstract

Breast cancer has become a leading cause of cancer-related deaths in women worldwide. DNA methylation has been revealed to play an enormously important role in the development and progression of breast cancer. DNA methylation is regulated by DNA methyltransferases (DNMTs), including DNMT1, DNMT2, and DNMT3. DNMT3 family has three members: DNMT3A, DNMT3B, and DNMT3L. The roles and functions of DNMT1 in breast cancer have been well reviewed. In this article, the roles of DNMT3A and DNMT3B in breast tumorigenesis and development are reviewed. We also discuss the SNP and mutations of DNMT3A and DNMT3B in breast cancer. In addition, we summarize how DNMT3A and DNMT3B are regulated by non-coding RNAs and signaling pathways in breast cancer, and targeting the expression levels of DNMT3A and DNMT3B may be a promising therapeutic approach for breast cancer. This review will provide reference for further studies on the biological functions and molecular mechanisms of DNMT3A and DNMT3B in breast cancer.

Endometriotic mesenchymal stem cells promote the fibrosis process of endometriosis through paracrine TGF‐β1 mediated RASAL1 inhibition

“…12 DNA methyltransferase 3A (DNMT3A) is a de novo methyltransferase necessary for mammalian development. 13 As previously illustrated, DNMT3A expression was markedly increased in the ectopic endometrium tissues of women with EMs. 14 In addition, the role of DNMT3A in regulating fibrosis has been widely studied.…”

“…DNA methylate modification is regulated by methyltransferase and demethylase 12 . DNA methyltransferase 3A (DNMT3A) is a de novo methyltransferase necessary for mammalian development 13 . As previously illustrated, DNMT3A expression was markedly increased in the ectopic endometrium tissues of women with EMs 14 .…”

Methyltransferase 3A-mediated promoter methylation represses retinoic acid receptor responder 3 expression in basal-like breast cancer

“…DNMT3A knockdown significantly restored RARRES3 expression at the mRNA and protein level in the two cell lines. DNMT3A overexpression has been widely reported in breast cancer (Man et al, 2022). Together with the basic helixloop-helix transcription factor (MYC), DNMT3A represses the transcription of miR-200b in triple-negative breast cancer cells (Pang et al, 2018).…”

Targeting polycomb repressor complex 2‐mediated bivalent promoter epigenetic silencing of secreted frizzled‐related protein 1 inhibits cholangiocarcinoma progression

“…DNMT1 is primarily responsible for maintaining methylation, while DNMT3a and DNMT3b are involved in de novo methylation. 22 DNMT3a/DNMT3b can actively introduce methylation into DNA to regulate gene expression, which plays a pivotal role in carcinogenesis. 23 Clinical data and gain-and loss-of-function studies have yielded evidence suggesting that EZH2 plays an oncogenic role in CCA.…”

“…Generally, DNMTs regulate DNA methylation, with three common isoforms identified in humans: DNMT1, DNMT3a and DNMT3b. DNMT1 is primarily responsible for maintaining methylation, while DNMT3a and DNMT3b are involved in de novo methylation 22 . DNMT3a/DNMT3b can actively introduce methylation into DNA to regulate gene expression, which plays a pivotal role in carcinogenesis 23 …”