MicroRNAs and prostate cancer

Coppola, Valeria; Maria, Ruggero De; Bonci, Desirée

doi:10.1677/erc-09-0172

Cited by 137 publications

(134 citation statements)

References 156 publications

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“…MiR-141 is found upregulated in primary tissues in a variety of studies including ours (2,25), and inclusion of miRNA expression data significantly improves the accuracy of markers like prostatespecific antigen in the diagnosis or prediction of tumor outcome (33). The induction of the miR-106b-93-25 cluster is in line with the poor prognosis described by others (34).…”

Section: Discussionmentioning

confidence: 81%

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

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MicroRNAs (miRNA) posttranscriptionally regulate gene expression and are important in tumorigenesis. Previous deep sequencing identified the miRNA profile of prostate carcinoma versus nonmalignant prostate tissue. Here, we generated miRNA expression profiles of prostate carcinoma by deep sequencing, with increasing tumor stage relative to corresponding nonmalignant and healthy prostate tissue, and detected clearly changed miRNA expression patterns. The miRNA profiles of the healthy and nonmalignant tissues were consistent with our previous findings, indicating a high fidelity of the method employed. In the tumors, quantitative real-time PCR (qRT-PCR) analysis of 40 paired samples of prostate carcinoma versus normal tissue revealed significant upregulation of miR-20a, miR-148a, miR-200b, and miR-375 and downregulation of miR-143 and miR-145. Hereby, miR-375 increased from normal to organ-confined tumors (pT2 pN0), slightly decreased in tumors with extracapsular growth (pT3 pN0), but was then expressed again at higher levels in lymph node metastasizing (pN1) tumors. The sequencing data for miR-375 were confirmed by Northern blotting and qRT-PCR. The regulation for other selected miRNAs could, however, not be confirmed by qRT-PCR in individual tumor stages. MiR-200b, in addition to miR-200c and miR-375 reduced the expression of SEC23A. Interestingly, miR-375, found by sequencing in pT2 upregulated by us and others in tumor versus normal tissue, and miR-15a, found by sequencing in pT2 and pT3 and in the metastasizing tumors, target the phosphatases PHLPP1 and PHLPP2, respectively. PHLPP1 and PHLPP2 dephosphorylate members of the AKT family of signal transducers, thereby inhibiting cell growth. Coexpression of miR-15a and miR-375 resulted in downregulation of PHLPP1/2 and strongly increased prostate carcinoma cell growth.Implications: These genomic data reveal relevant miRNAs in prostate cancer that may have biomarker and therapeutic potential. Mol Cancer Res; 12(2); 250-63. Ó2013 AACR. IntroductionProstate carcinoma is the second most frequently diagnosed malignancy and a leading cause of cancer-related death in men worldwide (1). The underlying mechanisms resulting in invasive growth after dissemination of the primary tumor from the initial site in the prostate are not completely understood. MicroRNAs (miRNAs) are now recognized as contributing factors to the induction, growth, and metastasis

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Section: Discussionmentioning

confidence: 81%

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

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“…At present, consistent data regarding alterations in the expression of miRNA in PCa are still limited (reviewed by Coppola et al, 2010) and studies addressing the genome-wide expression profiling of other small ncRNA in this malignancy are lacking. Here, we utilized Solexa Illumina Deep Sequencing to examine the entire spectrum of small ncRNA in PCa specimens, and further screened for changes in the expression of 723 miRNAs by microarray-profiling of 102 histologically confirmed malignant and non-malignant samples from prostatectomy, lymph node and TURP origin.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

et al. 2011

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Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA (ncRNA) species are associated with the development and progression of this malignancy. To assess the diversity and abundance of small ncRNAs in PCa, we analyzed the composition of the entire small transcriptome by Illumina/ Solexa deep sequencing. We further analyzed the micro-RNA (miRNA) expression signatures of 102 fresh-frozen patient samples during PCa progression by miRNA microarrays. Both platforms were cross-validated by quantitative reverse transcriptase-PCR. Besides the altered expression of several miRNAs, our deep sequencing analyses revealed strong differential expression of small nucleolar RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly, the majority of miRNAs included in the predictor also exhibit high sequence counts and concordant differential expression in Illumina PCa samples, supported by quantitative reverse transcriptase-PCR. Our findings provide miRNA expression signatures that may serve as an accurate tool for the diagnosis and prognosis of PCa.

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“…miRNAs miRNAs regulate normal processes of growth and development as well as pathogenic processes associated with cancer, and analyses of their expression patterns have been effective for stratifying human cancers (Lu et al 2005;Volinia et al 2006). Expression profiling studies of human prostate tumors and xenografts have suggested that the expression patterns of miRNAs may distinguish indolent from aggressive tumors (Porkka et al 2007;Ambs et al 2008;Ozen et al 2008;Coppola et al 2009;DeVere White et al 2009), and have implicated specific miRNAs in castration-resistant prostate cancer Sun et al 2009). Consistent with these findings, key enzymatic components of miRNA synthesis and processing such as Dicer are up-regulated during prostate tumor progression (Chiosea et al 2006;Ambs et al 2008;Poliseno et al 2010a), while functional analyses of mice with conditional deletion of Dicer support a role for miRNAs in prostate epithelial proliferation .…”

Section: Ezh2mentioning

confidence: 99%

Molecular genetics of prostate cancer: new prospects for old challenges

Shen¹,

Abate‐Shen²

2010

Genes Dev.

840

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Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Since early studies on the role of the androgen receptor that led to the advent of androgen deprivation therapy in the 1940s, there has long been intensive interest in the basic mechanisms underlying prostate cancer initiation and progression, as well as the potential to target these processes for therapeutic intervention. Here, we present an overview of major themes in prostate cancer research, focusing on current knowledge of principal events in cancer initiation and progression. We discuss recent advances, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics. Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead.

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MicroRNAs and prostate cancer

Cited by 137 publications

References 156 publications

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

Molecular genetics of prostate cancer: new prospects for old challenges

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