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The Interactions of microRNA and Epigenetic Modifications in Prostate Cancer.

Singh PK, Campbell MJ - Cancers (Basel) (2013)

Bottom Line: Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state.Changes in DNA methylation, altered histone modifications and miRNA expression are functionally associated with CaP initiation and progression.Given the importance and prevalence of these epigenetic events in CaP biology it is timely to understand further how different epigenetic components interact and influence each other.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Prashant.singh@roswellpark.org.

ABSTRACT
Epigenetic modifiers play important roles in fine-tuning the cellular transcriptome. Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state. Distortions of the epigenome have been reported in cancer initiation and progression. DNA methylation and histone modifications are principle components of this epigenome, but more recently it has become clear that microRNAs (miRNAs) are another major component of the epigenome. Interactions of these components are apparent in prostate cancer (CaP), which is the most common non-cutaneous cancer and second leading cause of death from cancer in the USA. Changes in DNA methylation, altered histone modifications and miRNA expression are functionally associated with CaP initiation and progression. Various aspects of the epigenome have also been investigated as biomarkers for different stages of CaP detection, though with limited success. This review aims to summarize key aspects of these mechanistic interactions within the epigenome and to highlight their translational potential as functional biomarkers. To this end, exploration of TCGA prostate cancer data revealed that expression of key CaP miRNAs inversely associate with DNA methylation. Given the importance and prevalence of these epigenetic events in CaP biology it is timely to understand further how different epigenetic components interact and influence each other.

No MeSH data available.


Related in: MedlinePlus

UCSC genome browser tracks showing CpG methylation and DNase I cleavage status around miRNAs. Top panel track shows the genomic location of the miRNA. Middle track shows the CpGs in genomic fragment and color of each CpG represent the beta values (ENCODE description—Orange, beta value equal to or greater than 0.6 was considered fully methylated; Purple, Beta values between 0.2 and 0.6 were considered to be partially methylated; Blue, beta value equal to or less than 0.2 was considered to be fully unmethylated). Bottom panel shows the DNaseI sensitivity measured in PrEC (black) and LNCaP (blue). DNaseI hypersensitive sites shown as peaks suggest accessible chromatin; conversely no DNaseI hypersensitive sites suggest closed chromatin. (A) Shows the status of miR-205. Most of the CpGs around miR-205 are partially methylated in LNCaP and un-methylated in PrEC. Supportively, DNaseI sensitivity shows open areas in PrEC cells and closed chromatin in LNCaP and. (B) Shows the status of a miR-17-92 cluster. Two CpGs around this cluster are partially methylated in PrEC cells and un-methylated in LNCaP. Supportively, DNaseI sensitivity shows open chromatin in LNCaP and closed in PrEC cells. Differentially methylated CpGs are underlined.
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cancers-05-00998-f003: UCSC genome browser tracks showing CpG methylation and DNase I cleavage status around miRNAs. Top panel track shows the genomic location of the miRNA. Middle track shows the CpGs in genomic fragment and color of each CpG represent the beta values (ENCODE description—Orange, beta value equal to or greater than 0.6 was considered fully methylated; Purple, Beta values between 0.2 and 0.6 were considered to be partially methylated; Blue, beta value equal to or less than 0.2 was considered to be fully unmethylated). Bottom panel shows the DNaseI sensitivity measured in PrEC (black) and LNCaP (blue). DNaseI hypersensitive sites shown as peaks suggest accessible chromatin; conversely no DNaseI hypersensitive sites suggest closed chromatin. (A) Shows the status of miR-205. Most of the CpGs around miR-205 are partially methylated in LNCaP and un-methylated in PrEC. Supportively, DNaseI sensitivity shows open areas in PrEC cells and closed chromatin in LNCaP and. (B) Shows the status of a miR-17-92 cluster. Two CpGs around this cluster are partially methylated in PrEC cells and un-methylated in LNCaP. Supportively, DNaseI sensitivity shows open chromatin in LNCaP and closed in PrEC cells. Differentially methylated CpGs are underlined.

Mentions: Recently published large scale ENCODE ChIP-seq data for various epigenetic features (e.g., histone marks, chromatin accessibility and DNA methylation) provide a key opportunity to study these associations in various cancer models including CaP [26,128]. Additionally, as an example, we also examined the chromatin accessibility around the miRNAs identified from regulome analysis in LNCaP and PrEC cells from ENCODE. As shown in Figure 3, miRNAs with higher expression in CaP tumors (miR-17, miR-20a and miR-92a) which were associated with low methylation also showed low methylation and open chromatin in LNCaP as compared to PrEC cells. Similarly, miRNA with low expression and high methylation in CaP tumors showed more methylation and closed chromatin in LNCaP (e.g., miR-205).


The Interactions of microRNA and Epigenetic Modifications in Prostate Cancer.

Singh PK, Campbell MJ - Cancers (Basel) (2013)

UCSC genome browser tracks showing CpG methylation and DNase I cleavage status around miRNAs. Top panel track shows the genomic location of the miRNA. Middle track shows the CpGs in genomic fragment and color of each CpG represent the beta values (ENCODE description—Orange, beta value equal to or greater than 0.6 was considered fully methylated; Purple, Beta values between 0.2 and 0.6 were considered to be partially methylated; Blue, beta value equal to or less than 0.2 was considered to be fully unmethylated). Bottom panel shows the DNaseI sensitivity measured in PrEC (black) and LNCaP (blue). DNaseI hypersensitive sites shown as peaks suggest accessible chromatin; conversely no DNaseI hypersensitive sites suggest closed chromatin. (A) Shows the status of miR-205. Most of the CpGs around miR-205 are partially methylated in LNCaP and un-methylated in PrEC. Supportively, DNaseI sensitivity shows open areas in PrEC cells and closed chromatin in LNCaP and. (B) Shows the status of a miR-17-92 cluster. Two CpGs around this cluster are partially methylated in PrEC cells and un-methylated in LNCaP. Supportively, DNaseI sensitivity shows open chromatin in LNCaP and closed in PrEC cells. Differentially methylated CpGs are underlined.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795376&req=5

cancers-05-00998-f003: UCSC genome browser tracks showing CpG methylation and DNase I cleavage status around miRNAs. Top panel track shows the genomic location of the miRNA. Middle track shows the CpGs in genomic fragment and color of each CpG represent the beta values (ENCODE description—Orange, beta value equal to or greater than 0.6 was considered fully methylated; Purple, Beta values between 0.2 and 0.6 were considered to be partially methylated; Blue, beta value equal to or less than 0.2 was considered to be fully unmethylated). Bottom panel shows the DNaseI sensitivity measured in PrEC (black) and LNCaP (blue). DNaseI hypersensitive sites shown as peaks suggest accessible chromatin; conversely no DNaseI hypersensitive sites suggest closed chromatin. (A) Shows the status of miR-205. Most of the CpGs around miR-205 are partially methylated in LNCaP and un-methylated in PrEC. Supportively, DNaseI sensitivity shows open areas in PrEC cells and closed chromatin in LNCaP and. (B) Shows the status of a miR-17-92 cluster. Two CpGs around this cluster are partially methylated in PrEC cells and un-methylated in LNCaP. Supportively, DNaseI sensitivity shows open chromatin in LNCaP and closed in PrEC cells. Differentially methylated CpGs are underlined.
Mentions: Recently published large scale ENCODE ChIP-seq data for various epigenetic features (e.g., histone marks, chromatin accessibility and DNA methylation) provide a key opportunity to study these associations in various cancer models including CaP [26,128]. Additionally, as an example, we also examined the chromatin accessibility around the miRNAs identified from regulome analysis in LNCaP and PrEC cells from ENCODE. As shown in Figure 3, miRNAs with higher expression in CaP tumors (miR-17, miR-20a and miR-92a) which were associated with low methylation also showed low methylation and open chromatin in LNCaP as compared to PrEC cells. Similarly, miRNA with low expression and high methylation in CaP tumors showed more methylation and closed chromatin in LNCaP (e.g., miR-205).

Bottom Line: Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state.Changes in DNA methylation, altered histone modifications and miRNA expression are functionally associated with CaP initiation and progression.Given the importance and prevalence of these epigenetic events in CaP biology it is timely to understand further how different epigenetic components interact and influence each other.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Prashant.singh@roswellpark.org.

ABSTRACT
Epigenetic modifiers play important roles in fine-tuning the cellular transcriptome. Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state. Distortions of the epigenome have been reported in cancer initiation and progression. DNA methylation and histone modifications are principle components of this epigenome, but more recently it has become clear that microRNAs (miRNAs) are another major component of the epigenome. Interactions of these components are apparent in prostate cancer (CaP), which is the most common non-cutaneous cancer and second leading cause of death from cancer in the USA. Changes in DNA methylation, altered histone modifications and miRNA expression are functionally associated with CaP initiation and progression. Various aspects of the epigenome have also been investigated as biomarkers for different stages of CaP detection, though with limited success. This review aims to summarize key aspects of these mechanistic interactions within the epigenome and to highlight their translational potential as functional biomarkers. To this end, exploration of TCGA prostate cancer data revealed that expression of key CaP miRNAs inversely associate with DNA methylation. Given the importance and prevalence of these epigenetic events in CaP biology it is timely to understand further how different epigenetic components interact and influence each other.

No MeSH data available.


Related in: MedlinePlus