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
January 2013
Oncogene;1/3/2013, Vol. 32 Issue 1, p127
Academic Journal
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.


Related Articles

  • A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors. Low, J S W; Tao, Q; Ng, K M; Goh, H K; Shu, X-S; Woo, W L; Ambinder, R F; Srivastava, G; Shamay, M; Chan, A T C; Popescu, N C; Hsieh, W-S // Oncogene;4/21/2011, Vol. 30 Issue 16, p1923 

    The critical 8p22 tumor suppressor deleted in liver cancer 1 (DLC1) is frequently inactivated by aberrant CpG methylation and/or genetic deletion and implicated in tumorigeneses of multiple tumor types. Here, we report the identification and characterization of its new isoform, DLC1 isoform 4...

  • DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation. Pellacani, D; Kestoras, D; Droop, A P; Frame, F M; Berry, P A; Lawrence, M G; Stower, M J; Simms, M S; Mann, V M; Collins, A T; Risbridger, G P; Maitland, N J // Cell Death & Differentiation;May2014, Vol. 21 Issue 5, p761 

    Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hypermethylation has been associated with gene...

  • Downregulation of EphA5 by promoter methylation in human prostate cancer. Shibao Li; Yingfeng Zhu; Chunguang Ma; Zhenhua Qiu; Xinju Zhang; Zhihua Kang; Zhiyuan Wu; Hua Wang; Xiao Xu; Hu Zhang; Guoqiang Ren; Jianmin Tang; Xiangyu Li; Ming Guan // BMC Cancer;2015, Vol. 15 Issue 1, p1 

    Background EphA5 is a member of the Eph/ephrin family and plays a critical role in the regulation of carcinogenesis. A significant reduction of EphA5 transcripts in high-grade prostate cancer tissue was shown using a transcriptomic analysis, compared to the low-grade prostate cancer tissue. As...

  • Genome-Wide Analysis of DNA Methylation and Expression of MicroRNAs in Breast Cancer Cells. Morita, Sumiyo; Takahashi, Ryou-u; Yamashita, Riu; Toyoda, Atsushi; Horii, Takuro; Kimura, Mika; Fujiyama, Asao; Nakai, Kenta; Tajima, Shoji; Matoba, Ryo; Ochiya, Takahiro; Hatada, Izuho // International Journal of Molecular Sciences;Jul2012, Vol. 13 Issue 7, p8259 

    DNA methylation of promoters is linked to transcriptional silencing of protein-coding genes, and its alteration plays important roles in cancer formation. For example, hypermethylation of tumor suppressor genes has been seen in some cancers. Alteration of methylation in the promoters of...

  • IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation. Smith, E; Ruszkiewicz, A R; Jamieson, G G; Drew, P A // British Journal of Cancer;2/4/2014, Vol. 110 Issue 3, p775 

    Background:We examined whether silencing of IGFBP7 was associated with survival in patients with oesophageal adenocarcinoma.Methods:Protein expression of IGFBP7 was determined using immunohistochemistry in a tissue microarray representing tumours from 65 patients with oesophageal adenocarcinoma...

  • Overexpression of ribosomal RNA in prostate cancer is common but not linked to rDNA promoter hypomethylation. Uemura, M; Zheng, Q; Koh, C M; Nelson, W G; Yegnasubramanian, S; De Marzo, A M // Oncogene;3/8/2012, Vol. 31 Issue 10, p1254 

    Alterations in nucleoli, including increased numbers, increased size, altered architecture and increased function are hallmarks of prostate cancer cells. The mechanisms that result in increased nucleolar size, number and function in prostate cancer have not been fully elucidated. The nucleolus...

  • Reduced expression of DACT2 promotes hepatocellular carcinoma progression: involvement of methylation-mediated gene silencing. Sheng Gao; Zhe Yang; Zheng, Zhi-Yun; Jia Yao; Feng Zhang; Wu, Li-Ming; Xie, Hai-Yang; Lin zhou; Zheng, Shu-Sen // World Journal of Surgical Oncology;2013, Vol. 11 Issue 1, p1 

    Background: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of HCC; however, the molecular mechanisms that lead to hepatocarcinogenesis and...

  • False-positive TUNEL staining observed in SV40 based transgenic murine prostate cancer models. Lawrence, M.; Blyth, B.; Ormsby, R.; Tilley, W.; Sykes, P. // Transgenic Research;Oct2013, Vol. 22 Issue 5, p1037 

    The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) and LADY (Probasin-large T antigen transgenic mouse) mice are widely used autochthonous models of prostate cancer. Both models utilise probasin promoters to direct androgen-regulated expression of oncogenic SV40 specifically to...

  • GSTP1 DNA Methylation and Expression Status Is Indicative of 5-aza-29-Deoxycytidine Efficacy in Human Prostate Cancer Cells. Chiam, Karen; Centenera, Margaret M.; Butler, Lisa M.; Tilley, Wayne D.; Bianco-Miotto, Tina // PLoS ONE;2011, Vol. 6 Issue 9, p1 

    DNA methylation plays an important role in carcinogenesis and the reversibility of this epigenetic modification makes it a potential therapeutic target. To date, DNA methyltransferase inhibitors (DNMTi) have not demonstrated clinical efficacy in prostate cancer, with one of the major obstacles...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics