Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells

Pan, Yu; Guo, Yawen; Maimaiti, Yusufu; Liu, Zeming; Wang, Shan; Yin, Xingjie; Peng, Gongling; Wang, Longqiang; Zhao, Xiangwang; Guo, Hui; Huang, Tao; Liu, Chunping

doi:10.1002/cbin.10646

Cited by 9 publications

(4 citation statements)

References 34 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In BC, silencing of EZH2 has been intensively shown to reduce the growth and metastasis of BC regardless of the subtypes (Han et al, 2018;Zhou et al, 2020). Mechanically, EZH2 has been reported to mediate the CpG island methylation of the RASSF2A promoter, therefore improving the activity of BC cells (Yu et al, 2016). Likewise, methylation modifications of EZH2 on miRNAs have also been implicated in human cancer progression (Ning et al, 2015;Kwon et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

et al. 2021

View full text Add to dashboard Cite

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.

show abstract

Section: Discussionmentioning

confidence: 99%

EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Changes in DNA methylation have been recognized as one of the most common molecular alterations in cancer [2]. Aberrant methylation patterns have been frequently reported in breast cancer, with studies primarily focused on promoter regions of protein-coding genes (PCGs) [3][4][5][6]. Specific methylation patterns have been associated with high tumor grade and ER negativity of breast cancer [4,[7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Differential methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry

et al. 2021

View full text Add to dashboard Cite

Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- subtype, and their functional role in the regulation of miRNA expression, especially among high risk AA women. In this study, we evaluated DNA methylation patterns of miRNA encoding genes and their effect on expression in breast tumors from both AA and EA women. The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, corresponding to 2,035 unique mature miRNAs. We identified differentially methylated loci (DMLs: (|delta β|)>0.10, FDR<0.05) between ER- and ER+ tumor subtypes, including 290 DMLs shared in both races, 317 and 136 were specific to AA and EA women, respectively. Integrated analysis identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs within miR-190b and miR-135b highly negatively correlated with their expression. These results were then validated in the TCGA dataset. Target prediction and pathway analysis showed that these DNA methylation-dysregulated miRNAs are involved in multiple cancer-related pathways, including cell cycle G1-S growth factor regulation, cytoskeleton remodeling, angiogenesis, EMT, and ESR1-mediated signaling pathways. In summary, our results suggest that DNA methylation changes within miRNA genes are associated with altered miRNA expression, which may contribute to the network of subtype- and race-related tumor biological differences in breast cancer. These findings support the involvement of epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes, which may serve as potential preventative and therapeutic targets.

show abstract

“…Changes in DNA methylation have been recognized as one of the most common molecular alterations in cancer (2). Aberrant methylation patterns have been frequently reported in breast cancer, with studies primarily focused on promoter regions of protein-coding genes (PCGs) (3)(4)(5)(6). Speci c methylation patterns have been associated with high tumor grade and ER negativity of breast cancer (4,(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry

Gong

Chen

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). The reasons remain largely unknown. Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- breast cancer, and their functional role in the regulation of miRNA expression, especially among high risk AA women. Methods: In this study, genome-wide DNA methylation and miRNA expression profiling was performed using the Illumina Infinium HumanMethylation450 Bead Chip platform and miRNA sequencing (miRNA-seq) in breast tumors from both AA and EA women. Results: The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, which correspond to 2,035 unique mature miRNAs. Cluster analysis of these miRNA-associated methylation loci showed a clear pattern of ER-subtype differences. We identified differentially methylated loci (DMLs: (|delta β|)>0.10, FDR<0.05) between ER- and ER+ tumor subtypes, including 290 DMLs shared in both races, 317 and 136 were specific to AA and EA women, respectively. Integrated analysis of DNA methylation and corresponding miRNA expression identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs within miR-190b and miR-135b highly negatively correlated with their expression. Further target prediction and pathway analysis showed that these DNA methylation-dysregulated miRNAs are involved in multiple cancer-related pathways, including cell cycle G1-S growth factor, cytoskeleton remodeling, angiogenesis, EMT, and others such as signal transduction TGF-β, Wnt, NOTCH, and ESR1-mediated signaling pathways. Conclusions: Our results suggest that DNA methylation changes within miRNA genes are associated with altered miRNA expression, which may contribute to the network of subtype- and race-related tumor biological differences in breast cancer. These findings shed light on the epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes and to serve as potential preventative and therapeutic targets.

show abstract

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells

Cited by 9 publications

References 34 publications

EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

Differential methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry

Genome-wide DNA methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry

Contact Info

Product

Resources

About