DNA methylation silences miR-132 in prostate cancer

A. Formosa, A. M. Lena, E. K. Markert, S. Cortelli, R. Miano, A. Mauriello, N. Croce, J. Vandesompele, P. Mestdagh, E. Finazzi-Agrò, A. J. Levine, G. Melino, S. Bernardini, E. Candi

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Silencing of microRNAs (miRNAs) by promoter CpG island methylation may be an important mechanism in prostate carcinogenesis. To screen for epigenetically silenced miRNAs in prostate cancer (PCa), we treated prostate normal epithelial and carcinoma cells with 5-aza-2′-deoxycytidine (AZA) and subsequently examined expression changes of 650 miRNAs by megaplex stemloop reverse transcription-quantitative PCR. After applying a selection strategy, we analyzed the methylation status of CpG islands upstream to a subset of miRNAs by methylation-specific PCR. The CpG islands of miR-18b, miR-132, miR-34b/c, miR-148a, miR-450a and miR-542-3p showed methylation patterns congruent with their expression modulations in response to AZA. Methylation analysis of these CpG islands in a panel of 50 human prostate carcinoma specimens and 24 normal controls revealed miR-132 to be methylated in 42% of human cancer cases in a manner positively correlated to total Gleason score and tumor stage. Expression analysis of miR-132 in our tissue panel confirmed its downregulation in methylated tumors. Re-expression of miR-132 in PC3 cells induced cell detachment followed by cell death (anoikis). Two pro-survival proteins - heparin-binding epidermal growth factor and TALIN2 - were confirmed as direct targets of miR-132. The results of this study point to miR-132 as a methylation-silenced miRNA with an antimetastatic role in PCa controlling cellular adhesion.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalOncogene
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 3 2013

Fingerprint

DNA Methylation
Methylation
Prostatic Neoplasms
MicroRNAs
CpG Islands
decitabine
Prostate
Anoikis
Carcinoma
Neoplasms
Polymerase Chain Reaction
Neoplasm Grading
Epidermal Growth Factor
Reverse Transcription
Carcinogenesis
Cell Death
Down-Regulation
Epithelial Cells
Survival

Keywords

  • anoikis
  • methylation
  • methylation-specific PCR
  • miR-132
  • miRNAs
  • prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Formosa, A., Lena, A. M., Markert, E. K., Cortelli, S., Miano, R., Mauriello, A., ... Candi, E. (2013). DNA methylation silences miR-132 in prostate cancer. Oncogene, 32(1), 127-134. https://doi.org/10.1038/onc.2012.14

DNA methylation silences miR-132 in prostate cancer. / Formosa, A.; Lena, A. M.; Markert, E. K.; Cortelli, S.; Miano, R.; Mauriello, A.; Croce, N.; Vandesompele, J.; Mestdagh, P.; Finazzi-Agrò, E.; Levine, A. J.; Melino, G.; Bernardini, S.; Candi, E.

In: Oncogene, Vol. 32, No. 1, 03.01.2013, p. 127-134.

Research output: Contribution to journalArticle

Formosa, A, Lena, AM, Markert, EK, Cortelli, S, Miano, R, Mauriello, A, Croce, N, Vandesompele, J, Mestdagh, P, Finazzi-Agrò, E, Levine, AJ, Melino, G, Bernardini, S & Candi, E 2013, 'DNA methylation silences miR-132 in prostate cancer', Oncogene, vol. 32, no. 1, pp. 127-134. https://doi.org/10.1038/onc.2012.14
Formosa A, Lena AM, Markert EK, Cortelli S, Miano R, Mauriello A et al. DNA methylation silences miR-132 in prostate cancer. Oncogene. 2013 Jan 3;32(1):127-134. https://doi.org/10.1038/onc.2012.14
Formosa, A. ; Lena, A. M. ; Markert, E. K. ; Cortelli, S. ; Miano, R. ; Mauriello, A. ; Croce, N. ; Vandesompele, J. ; Mestdagh, P. ; Finazzi-Agrò, E. ; Levine, A. J. ; Melino, G. ; Bernardini, S. ; Candi, E. / DNA methylation silences miR-132 in prostate cancer. In: Oncogene. 2013 ; Vol. 32, No. 1. pp. 127-134.
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