Androgen receptor is negatively correlated with the methylation-mediated transcriptional repression of miR-375 in human prostate cancer cells

Chu, Mingliang; Chang, Yunli; Li, Ping; Guo, Yanjing; Zhang, Kaiqing; Gao, Wei‐Qiang

doi:10.3892/or.2013.2810

Cited by 34 publications

(40 citation statements)

References 30 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, our gene set enrichment analysis analysis revealed that miR-375 is positively correlated with androgen signalling in multiple tumor data sets (Supplementary Figure 9). A molecular mechanism that potentially underpins this association was recently elucidated by Chu et al, 42 who demonstrated that the androgen receptor (AR) indirectly promotes miR-375 transcription by suppressing DNA methylation of its promoter. Thus, miR-375 may also serve as a proxy for AR activity and PSA levels, which are themselves prognostic in prostate cancer.…”

Section: Discussionmentioning

confidence: 98%

A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer

et al. 2016

View full text Add to dashboard Cite

MicroRNA-375 (miR-375) is frequently elevated in prostate tumors and cell-free fractions of patient blood, but its role in genesis and progression of prostate cancer is poorly understood. In this study, we demonstrated that miR-375 is inversely correlated with epithelial-mesenchymal transition signatures (EMT) in clinical samples and can drive mesenchymal-epithelial transition (MET) in model systems. Indeed, miR-375 potently inhibited invasion and migration of multiple prostate cancer lines. The transcription factor YAP1 was found to be a direct target of miR-375 in prostate cancer. Knockdown of YAP1 phenocopied miR-375 overexpression, and overexpression of YAP1 rescued anti-invasive effects mediated by miR-375. Furthermore, transcription of the miR-375 gene was shown to be directly repressed by the EMT transcription factor, ZEB1. Analysis of multiple patient cohorts provided evidence for this ZEB1-miR-375-YAP1 regulatory circuit in clinical samples. Despite its anti-invasive and anti-EMT capacities, plasma miR-375 was found to be correlated with circulating tumor cells in men with metastatic disease. Collectively, this study provides new insight into the function of miR-375 in prostate cancer, and more broadly identifies a novel pathway controlling epithelial plasticity and tumor cell invasion in this disease.

show abstract

Section: Discussionmentioning

confidence: 98%

A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Chu et al found that there existed the negative correlation between AR and total DNMT activity, indicating that DNMTs are such responder for this process and can be negatively controlled by AR. 13) In addition, ART could induce the marked sustained increase of [Ca 2+ ] i , and subsequently triggered the apoptosis of prostatic cancer cells. 24) While DNMT3b resulted in the increase in apoptosis of prostatic cancer cells, DNMT3b should be positively related to ART, which was approved by our analysis of DNMTs expression of PCa tumor and PCa cells that both of the expression and the catalytic activity of DNMT3b were upregulated when AR was restrained in the presence of ART.…”

Section: Discussionmentioning

confidence: 99%

“…12) Interestingly, DNMTs activity can be negatively regulated by AR in human prostate cancer cells. 13) Therefore, the present study used the prostatic cancer cells 22rv1 and investigated the effects of ART on the growth in mice and cell viability and apoptosis in vitro, and the expressions of AR and DNMTs as well, aiming to demonstrate the role of AR and it regulated DNMTs in anti-PCa action of ART.…”

mentioning

confidence: 99%

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor

Wang¹,

Wang²,

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Prostatic cancer (PCa) is a leading cause of cancer related death in males and is often regarded as a kind of androgen-sensitive cancer. Artesunate (ART), a semi-synthetic derivative of the Chinese herb Artemisia annua, is such an anti-cancer agent. However, the effects and mechanism of ART on PCa cells remains unclear. The study aims to elaborate the mechanism of the involvement of androgen receptor (AR) in antiprostatic cancer (PCa) of artesunate (ART). PCa cells 22rvl were used in vivo and in vitro, and the viability and apoptosis were conducted using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. Ectopic expressions of AR and DNA methyltransferase (DNMT) were detected in cells in overexpression or interference of AR or DNMT3b. ART dose-dependently suppressed tumor growth, inhibited cell viability, enhanced apoptosis, decreased AR expression, and increased the expression and the catalytic activity of DNMT3b in 22rv1 cells either in transplanted mice or in vitro. Furthermore, AR downregulated DNMT3b expression, and overexpression of AR or interference of DNMT3b could reverse ART-induced cytotoxicity and apoptosis in 22rvl cells, whereas overexpression of DNMT3b could not change the effect profiles of ART on the cells. The results indicated that ART suppressed tumor growth of prostatic cancer cells through AR-DNMT3b pathway, underlying ART will allow for the utilization of this Chinese therapeutic agent for the potential treatment of prostate cancer.Key words artesunate; prostatic cancer; androgen receptor; DNA methyltransferase; apoptosis Prostatic cancer (PCa) is the most common cause of cancerrelated death in males. Morbidity and mortality of PCa underscore the need for novel treatment options. Although improved therapies have been recently developed to treat and prevent PCa, prostate cancer still remains refractory disease. Lately, herbs and phytochemicals 1) have been attractive as therapeutic agents for tumorigenesis suppression. Understanding how the production of these Chinese herbs is regulated during cancer progression would help develop new cancer therapeutic strategy.Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART has been revealed remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. With the recognition of ART, it has now been analyzed for its anti-cancer activity in various tissues-specificity. For example, Tran et al. found that enhancement of ART activity could effectively induce the apoptosis of breast cancer cells. 2)Moreover, ART was proved to be as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation action on tumor growth, metastasis.3) Recently, Michaelsen et al. clinically treated PCa patients with long-term Artemisia annua capsules via oral administration combined with shortterm ART inj...

show abstract

“…Of these differentially methylated sequences detected by MCAM, we selected four genes (GAS6, GAD2, MAP6, and CNN3) for validation on the basis of several criteria: a P-value less than 0.01, only probes located in the CGIs, probes with a frequency of 70% in one group and less than 30% in the other, gene function, and confirmation that the gene was methylated in the AR ¡ SCPC patient samples analyzed by the Illumina 450K array. Additionally, we chose to validate TMPRSS2 solely on the basis of results from the Illumina arrays because of gene function and previous reports of methylation status in AR-negative prostate cancer cell lines 23 We then used pyrosequencing to quantify the methylation levels of these genes in the xenograft samples (Fig. 2B).…”

Section: Differences In Dna Methylation Profiles Between Armentioning

confidence: 99%

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas

et al. 2016

View full text Add to dashboard Cite

(2016) Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas, Epigenetics, 11:3, 184-193, DOI: 10.1080/15592294.2016 ABSTRACTSmall cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR ¡ SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR C ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR ¡ and AR C PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR ¡ SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR ¡ SCPC cell lines. We conclude that the epigenome of AR ¡ is distinct from that of AR C castration-resistant prostate carcinomas, and that the AR ¡ phenotype can be reversed with epigenetic drugs.

show abstract

Androgen receptor is negatively correlated with the methylation-mediated transcriptional repression of miR-375 in human prostate cancer cells

Cited by 34 publications

References 30 publications

A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer

A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer

<i>Artesunate</i> Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas

Contact Info

Product

Resources

About