Epigenetics in Breast and Prostate Cancer

Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

doi:10.1007/978-1-4939-1804-1_23

Cited by 94 publications

(57 citation statements)

References 114 publications

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“…This suggests that Mfn2 hypoexpression in breast cancer is at least partially attributable to hypermethylaton of its promoter. Although 5-aza-CdR can rescue the expression of tumor suppressor genes by demethylating their promoter CpG sites (24)(25)(26)(27)(28)(29)(30)(31), its clinical anti-tumor applications are limited due to lack of gene specificity. Furthermore, it was reported that Mfn2 is a direct target of miR-761 and upregulation of Mfn2 expression by inhibiting miR-761 repressed hepatocarcinoma growth and metastasis (32).…”

Section: Discussionmentioning

confidence: 99%

The anti-tumor effects of Mfn2 in breast cancer are dependent on promoter DNA methylation, the P21Ras motif and PKA phosphorylation site

Dong

Shan

et al. 2018

Oncol Lett

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Abstract. Mitofusin 2 (Mfn2) is expressed in numerous human tissues and serves a pivotal role in cell proliferation. However, Mfn2 is considered as an anti-tumor gene, and is silenced in human malignant tumors, including those of breast cancer. However, the mechanisms contributing to Mfn2 silencing and the mechanism of its anti-tumor function in breast cancer remain unclear. In the present study, hypoexpression of Mfn2, and hypermethylation of its promoter, was confirmed in human breast cancer cells and in breast cancer tissues by reverse transcription-quantitative polymerase chain reaction (PCR) and methylation specific PCR, respectively. Chemical demethylation treatment with 5-aza-2'-deoxycytidine upregulated the mRNA expression level of Mfn2 in MCF-7 cells in a dose-dependent manner. In addition, overexpression of Mfn2 repressed the proliferation, migration and invasion of MCF-7 cells, mediated by inhibition of the Ras-extracellular signal-regulated kinase (ERK)1/2 signaling pathway. However, overexpression of Mfn2 with deletion of the p21Ras motif (Mfn2 ΔRas ) and protein kinase A (PKA) phosphorylation site (Mfn2 ΔPKA ) partially reduced the anti-tumor function of Mfn2, and inhibited the Ras-ERK1/2 signaling pathway. Taken together, the present study confirmed the anti-tumor effects of Mfn2 in human breast cancer and clarified that the mechanism of its anti-tumor functions includes promoter DNA methylation, the P21 Ras binding site and PKA phosphorylation.

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Section: Discussionmentioning

confidence: 99%

The anti-tumor effects of Mfn2 in breast cancer are dependent on promoter DNA methylation, the P21Ras motif and PKA phosphorylation site

Dong

Shan

et al. 2018

Oncol Lett

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“…175 In various cancer models, aberrant DNA and histone modifications have been shown to silence tumor suppressors or promote oncogenes. 176 The three major epigenetic modifications, namely DNA methylation, changes to chromatin, and noncoding RNA profiles, are discussed in this chapter.…”

Section: Epigenetic Basis Of Tcmmentioning

confidence: 99%

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science

et al. 2019

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Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine‐derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. In addition, the impact of TCM treatment on DNA methylation, histone modification, and the regulation of noncoding RNAs is discussed. Furthermore, we have highlighted studies of TCM therapy that modulate the tumor microenvironment and eliminate cancer stem cells. The information compiled in this review will serve as a solid foundation to formulate hypotheses for future studies on TCM‐based cancer therapy.

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“…Aberrant DNA hypermethylation of promoter‐associated CpG islands is characteristic for tumor cells, including PC cells (Jones and Laird, ; Baylin and Herman, ). Promoter hypermethylation is closely associated with gene silencing and may cause downregulation of, for example, tumor suppressor genes during carcinogenesis (Kulis and Esteller, ; Wu et al ., ). Moreover, aberrant promoter hypermethylation of specific genes has been reported to hold promising diagnostic and/or prognostic biomarker potential for PC in tissue samples (Park, ; Sorensen et al ., , ; Strand et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

et al. 2018

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Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, leading to overdiagnosis and overtreatment. Aberrant promoter hypermethylation of specific genes has been suggested as novel candidate biomarkers for PC that may improve diagnosis and prognosis. We here analyzed ST6GALNAC3 and ZNF660 promoter methylation in prostate tissues, and ST6GALNAC3,ZNF660,CCDC181, and HAPLN3 promoter methylation in liquid biopsies. First, using four independent patient sample sets, including a total of 110 nonmalignant (NM) and 705 PC tissue samples, analyzed by methylation‐specific qPCR or methylation array, we found that hypermethylation of ST6GALNAC3 and ZNF660 was highly cancer‐specific with areas under the curve (AUC) of receiver operating characteristic (ROC) curve analysis of 0.917–0.995 and 0.846–0.903, respectively. Furthermore, ZNF660 hypermethylation was significantly associated with biochemical recurrence in two radical prostatectomy (RP) cohorts of 158 and 392 patients and remained significant also in the subsets of patients with Gleason score ≤7 (univariate Cox regression and log‐rank tests, P < 0.05), suggesting that ZNF660 methylation analysis can potentially help to stratify low‐/intermediate‐grade PCs into indolent vs. more aggressive subtypes. Notably, ZNF660 hypermethylation was also significantly associated with poor overall and PC‐specific survival in the RP cohort (n = 158) with long clinical follow‐up available. Moreover, as proof of principle, we successfully detected highly PC‐specific hypermethylated circulating tumor DNA (ctDNA) for ST6GALNAC3,ZNF660,HAPLN3, and CCDC181 in liquid biopsies (serum) from 27 patients with PC vs. 10 patients with BPH, using droplet digital methylation‐specific PCR analysis. Finally, we generated a three‐gene (ST6GALNAC3/CCDC181/HAPLN3) ctDNA hypermethylation model, which detected PC with 100% specificity and 67% sensitivity. In conclusion, we here for the first time demonstrate diagnostic biomarker potential of ST6GALNAC3 and ZNF660 methylation, as well as prognostic biomarker potential of ZNF660. Furthermore, we show that hypermethylation of four genes can be detected in ctDNA in liquid biopsies (serum) from patients with PC.

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Epigenetics in Breast and Prostate Cancer

Cited by 94 publications

References 114 publications

The anti-tumor effects of Mfn2 in breast cancer are dependent on promoter DNA methylation, the P21Ras motif and PKA phosphorylation site

The anti-tumor effects of Mfn2 in breast cancer are dependent on promoter DNA methylation, the P21Ras motif and PKA phosphorylation site

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

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