MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma

Boll, Kerstin; Reiche, Kristin; Kasack, Katharina; Mörbt, Nora; Kretzschmar, A.; Tomm, Janina M.; Verhaegh, Gerald W.; Schalken, Jack A.; Bergen, Martin von; Horn, Friedemann; Hackermüller, Jörg

doi:10.1038/onc.2012.55

Cited by 204 publications

(176 citation statements)

References 51 publications

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“…1B). A strong downregulation of miR-205 in prostate carcinoma was also observed by Boll and colleagues (17). We again noted reduced levels of miRNAs like miR-143, miR-145, miR-320a, or miR-424 as previously described (5).…”

Section: Mirna Profiling Of Normal Prostate Tissues and Prostate Carcsupporting

confidence: 61%

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: Mirna Profiling Of Normal Prostate Tissues and Prostate Carcsupporting

confidence: 61%

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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“…The data revealed that the expression level of miR-203 was significantly reduced in NB tissues compared with their matched adjacent normal tissues, suggesting that the aberrant downregulation of miR-203 may be involved in the development and progression of NB. In fact, deregulation of miR-203 has been demonstrated to be associated with various cancer types, including hepatocellular carcinoma, pancreatic cancer, glioma, lung cancer, cervical cancer, prostate carcinoma, melanoma, esophageal squamous cell carcinoma and colon cancer (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The present study further revealed that the overexpression of miR-203 markedly suppressed the proliferation, migration and invasion of the SK-N-SH and SH-SY5Y NB cells, similar to the effects of Sam68 downregulation.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Zhao

Tian

et al. 2015

Molecular Medicine Reports

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Abstract. Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR-203 and increased expression of Sam68 co-existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK-N-SH and SH-SY5Y NB cells. Similarly, overexpression of miR-203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR-203 in the SK-N-SH and SH-SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR-203 directly targeted Sam68 by binding to its 3'-untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR-203 may contribute to the aberrant upregulation of Sam68 in NB and that miR-203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB.

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“…In addition to miR-29b, the VEGF transcript is predicted to contain binding sites for multiple miRNA types (as highlighted in Fig. 2C), such as miR-145 and miR-205, the expressions of which are reduced in PCa and have been shown to regulate VEGF in other cancer types (Szczyrba et al 2010, Fan et al 2012, Yue et al 2012, Boll et al 2013. However, it remains to be determined how effectively these miRNAs repress VEGF translation in PCa.…”

Section: Post-transcriptional Regulation Of Vegf Signaling In Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma

Cited by 204 publications

References 51 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

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Regulation of vascular endothelial growth factor in prostate cancer

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