EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER

Seodhna Lynch, Karla O'Neill, michael mckenna, Colum Walsh, Declan McKenna

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

MicroRNAs are small, non-coding RNA species (19-25nts) which have been found to play a fundamental role in many molecular pathways including embryogenesis, cell differentiation, proliferation and apoptosis. Altered miRNA expression has been correlated with a wide range of disease states and pathologies, including cancer. Recently, there is an increasing body of evidence suggesting that epigenetic regulation of miRNAs via DNA methylation may be an important mechanism in contributing to their deregulation in cancer. We hypothesise that miRNAs with tumour suppressor function may be silenced by epigenetic modifications in prostate cancer (PCa).In this study we have carried out a screen for miRNAs showing altered expression in PCa cell lines. This identified three miRNAs (miR-205, miR-200c, miR-138) that are typically down-regulated in PCa cells and which may be controlled by methylation. We also show that the expression of these miRNAs is generally decreased in prostate tumour biopsy samples compared to matched normal tissue. We demonstrate that these miRNAs are up-regulated by the chemotherapy drug decitabine (5-aza-2’deoxycytidine), which alters DNA methylation levels, and also by reduction in DNA methyltransferase 1 (DNMT1) levels in PCa cells. Methylation levels in the loci of each candidate miRNA were examined in PCa cells and biopsy tissue. We propose that the relative expression of these miRNAs is related to their respective methylation status. In addition, the functionality of the miRNAs in PCa cells has been investigated by examining their effect on cell proliferation, and by measuring expression levels of known and novel target genes. Our findings provide further evidence that profiling of miRNA expression and methylation status has great potential as a basis for a novel biomarker in the diagnosis and prognosis of PCa.
LanguageEnglish
Title of host publicationUnknown Host Publication
Number of pages35
Publication statusPublished - Mar 2014
EventRNAi 2014: Short and Long Non-coding RNAs - St Hilda's College, Oxford, UK
Duration: 1 Mar 2014 → …

Conference

ConferenceRNAi 2014: Short and Long Non-coding RNAs
Period1/03/14 → …

Fingerprint

MicroRNAs
Epigenomics
Prostatic Neoplasms
decitabine
Methylation
DNA Methylation
Neoplasms
Cell Proliferation
Biopsy
Small Untranslated RNA
Methyltransferases
Embryonic Development
Prostate
Cell Differentiation
Biomarkers
Apoptosis
Pathology
Drug Therapy
Cell Line

Keywords

  • epigenetic
  • microRNA
  • prostate cancer

Cite this

Lynch, S., O'Neill, K., mckenna, M., Walsh, C., & McKenna, D. (2014). EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER. In Unknown Host Publication
Lynch, Seodhna ; O'Neill, Karla ; mckenna, michael ; Walsh, Colum ; McKenna, Declan. / EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER. Unknown Host Publication. 2014.
@inproceedings{91234d5e6aeb40e1a53b6ba415d1750b,
title = "EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER",
abstract = "MicroRNAs are small, non-coding RNA species (19-25nts) which have been found to play a fundamental role in many molecular pathways including embryogenesis, cell differentiation, proliferation and apoptosis. Altered miRNA expression has been correlated with a wide range of disease states and pathologies, including cancer. Recently, there is an increasing body of evidence suggesting that epigenetic regulation of miRNAs via DNA methylation may be an important mechanism in contributing to their deregulation in cancer. We hypothesise that miRNAs with tumour suppressor function may be silenced by epigenetic modifications in prostate cancer (PCa).In this study we have carried out a screen for miRNAs showing altered expression in PCa cell lines. This identified three miRNAs (miR-205, miR-200c, miR-138) that are typically down-regulated in PCa cells and which may be controlled by methylation. We also show that the expression of these miRNAs is generally decreased in prostate tumour biopsy samples compared to matched normal tissue. We demonstrate that these miRNAs are up-regulated by the chemotherapy drug decitabine (5-aza-2’deoxycytidine), which alters DNA methylation levels, and also by reduction in DNA methyltransferase 1 (DNMT1) levels in PCa cells. Methylation levels in the loci of each candidate miRNA were examined in PCa cells and biopsy tissue. We propose that the relative expression of these miRNAs is related to their respective methylation status. In addition, the functionality of the miRNAs in PCa cells has been investigated by examining their effect on cell proliferation, and by measuring expression levels of known and novel target genes. Our findings provide further evidence that profiling of miRNA expression and methylation status has great potential as a basis for a novel biomarker in the diagnosis and prognosis of PCa.",
keywords = "epigenetic, microRNA, prostate cancer",
author = "Seodhna Lynch and Karla O'Neill and michael mckenna and Colum Walsh and Declan McKenna",
year = "2014",
month = "3",
language = "English",
booktitle = "Unknown Host Publication",

}

Lynch, S, O'Neill, K, mckenna, M, Walsh, C & McKenna, D 2014, EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER. in Unknown Host Publication. RNAi 2014: Short and Long Non-coding RNAs, 1/03/14.

EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER. / Lynch, Seodhna; O'Neill, Karla; mckenna, michael; Walsh, Colum; McKenna, Declan.

Unknown Host Publication. 2014.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER

AU - Lynch, Seodhna

AU - O'Neill, Karla

AU - mckenna, michael

AU - Walsh, Colum

AU - McKenna, Declan

PY - 2014/3

Y1 - 2014/3

N2 - MicroRNAs are small, non-coding RNA species (19-25nts) which have been found to play a fundamental role in many molecular pathways including embryogenesis, cell differentiation, proliferation and apoptosis. Altered miRNA expression has been correlated with a wide range of disease states and pathologies, including cancer. Recently, there is an increasing body of evidence suggesting that epigenetic regulation of miRNAs via DNA methylation may be an important mechanism in contributing to their deregulation in cancer. We hypothesise that miRNAs with tumour suppressor function may be silenced by epigenetic modifications in prostate cancer (PCa).In this study we have carried out a screen for miRNAs showing altered expression in PCa cell lines. This identified three miRNAs (miR-205, miR-200c, miR-138) that are typically down-regulated in PCa cells and which may be controlled by methylation. We also show that the expression of these miRNAs is generally decreased in prostate tumour biopsy samples compared to matched normal tissue. We demonstrate that these miRNAs are up-regulated by the chemotherapy drug decitabine (5-aza-2’deoxycytidine), which alters DNA methylation levels, and also by reduction in DNA methyltransferase 1 (DNMT1) levels in PCa cells. Methylation levels in the loci of each candidate miRNA were examined in PCa cells and biopsy tissue. We propose that the relative expression of these miRNAs is related to their respective methylation status. In addition, the functionality of the miRNAs in PCa cells has been investigated by examining their effect on cell proliferation, and by measuring expression levels of known and novel target genes. Our findings provide further evidence that profiling of miRNA expression and methylation status has great potential as a basis for a novel biomarker in the diagnosis and prognosis of PCa.

AB - MicroRNAs are small, non-coding RNA species (19-25nts) which have been found to play a fundamental role in many molecular pathways including embryogenesis, cell differentiation, proliferation and apoptosis. Altered miRNA expression has been correlated with a wide range of disease states and pathologies, including cancer. Recently, there is an increasing body of evidence suggesting that epigenetic regulation of miRNAs via DNA methylation may be an important mechanism in contributing to their deregulation in cancer. We hypothesise that miRNAs with tumour suppressor function may be silenced by epigenetic modifications in prostate cancer (PCa).In this study we have carried out a screen for miRNAs showing altered expression in PCa cell lines. This identified three miRNAs (miR-205, miR-200c, miR-138) that are typically down-regulated in PCa cells and which may be controlled by methylation. We also show that the expression of these miRNAs is generally decreased in prostate tumour biopsy samples compared to matched normal tissue. We demonstrate that these miRNAs are up-regulated by the chemotherapy drug decitabine (5-aza-2’deoxycytidine), which alters DNA methylation levels, and also by reduction in DNA methyltransferase 1 (DNMT1) levels in PCa cells. Methylation levels in the loci of each candidate miRNA were examined in PCa cells and biopsy tissue. We propose that the relative expression of these miRNAs is related to their respective methylation status. In addition, the functionality of the miRNAs in PCa cells has been investigated by examining their effect on cell proliferation, and by measuring expression levels of known and novel target genes. Our findings provide further evidence that profiling of miRNA expression and methylation status has great potential as a basis for a novel biomarker in the diagnosis and prognosis of PCa.

KW - epigenetic

KW - microRNA

KW - prostate cancer

M3 - Conference contribution

BT - Unknown Host Publication

ER -

Lynch S, O'Neill K, mckenna M, Walsh C, McKenna D. EPIGENETIC REGULATION OF MICRORNA EXPRESSION IN PROSTATE CANCER. In Unknown Host Publication. 2014