MiRNA profiles of prostate carcinoma detected by multi-platform miRNA screening. Int J Cancer

University Clinic of Urology, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
International Journal of Cancer (Impact Factor: 5.01). 02/2012; 130(3):611-21. DOI: 10.1002/ijc.26064
Source: PubMed

ABSTRACT MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in tumorigenesis. To characterize the diagnostic potential of miRNAs in prostate cancer, a leading cause of cancer mortality, we performed screening of miRNA expression profiles. We used commercially available microarrays to establish miRNA expression profiles from a cohort of 20 cancer samples. The expression of selected miRNAs was analyzed by quantitative real-time PCR and the identity of miRNA expressing cells was determined by miRNA in situ hybridization. We identified 25 miRNAs that showed a significant differential expression in cancer samples. The comparison with previously published data generated by deep sequencing of cDNA libraries of small RNA molecules revealed a concordance rate of 47% among miRNAs identified with both techniques. The differential expression of miRNAs miR-375, miR-143 and miR-145 was validated by quantitative PCR. MiRNA in situ hybridization revealed that the differential expression is cancer-cell associated. A combination of three miRNAs correctly classified tissue samples with an accuracy of 77.6% with an area under the receiver-operator characteristic curve of 0.810. Our data extend the knowledge about the deregulation of miRNAs in prostate cancer. The differential expression of several miRNAs is highly consistent using independent cohorts of tumor samples, different tissue preservation methods and different experimental methods. Our results indicate that combinations of miRNAs are promising biomarkers for the diagnosis of prostate cancer.

  • Source
    • "Of the four, miR-143, miR-145, and miR- 375 were best at distinguishing between malignant and nonmalignant tumors. Considering the three in conjunction, they were able to correctly distinguish between malignant and nonmalignant samples 77.6% of the time [17]. If a cancer type already has a standard method of subtype characterization it is possible for researchers to develop a miRNA screen around the molecular markers used for diagnosis; this was employed by Leivonen et al. with HER2 positive breast cancer lines and two patient cohorts. "
    [Show abstract] [Hide abstract]
    ABSTRACT: First discovered in 1993, microRNAs (miRNAs) have been one of the hottest research areas over the past two decades. Oftentimes, miRNAs levels are found to be dysregulated in cancer patients. The potential use of miRNAs in cancer therapies is an emerging and promising field, with research finding miRNAs to play a role in cancer initiation, tumor growth, and metastasis. Therefore, miRNAs could become an integral part from cancer diagnosis to treatment in future. This review aims to examine current novel research work on the potential roles of miRNAs in cancer therapies, while also discussing several current challenges and needed future research.
    BioMed Research International 07/2014; 2014:959461. DOI:10.1155/2014/959461 · 2.71 Impact Factor
  • Source
    • "A recent study found that miR- 200b is involved in arsenic (As) carcinogenesis (Wang et al., 2011b), indicating that miRNAs may have roles in environmental carcinogenesis. miR-143 is generally downregulated in colon cancer, liposarcoma, esophageal squamous cell carcinoma, and prostate cancer, suggesting that it has tumor-suppressive properties (Roa et al., 2010; Ugras et al., 2011; Wach et al., 2012; Wu et al., 2011). In this study, we established an in vitro model by transforming nontumorigenic human lung epithelial BEAS-2B cells through long-term exposure to Cr (VI). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hexavalent chromium [Cr (VI)] is a well-known human carcinogen associated with the increased risk of lung cancer. However, the mechanism underlying the Cr (VI)-induced carcinogenesis remains unclear due to the lack of suitable experimental models. In this study, we developed an in vitro model by transforming non-tumorigenic human lung epithelial BEAS-2B cells through long-term exposure to Cr (VI). By utilizing this model, we found that miR-143 expression levels were dramatically repressed in Cr (VI)- transformed cells. The repression of miR-143 led to Cr (VI)-induced cell malignant transformation and angiogenesis via up-regulation of IGF-IR and IRS1 expression. Moreover, we found that IL-8 is the major upregulated angiogenesis factor induced by Cr (VI) through activation of IGF-IR/IRS1 axis followed by activation of downstream ERK/HIF/NF-κB signaling pathway. These findings establish a causal role and mechanism of miR-143 in regulating Cr (VI)-induced malignant transformation and tumor angiogenesis.
    Toxicological Sciences 06/2013; 134(1). DOI:10.1093/toxsci/kft101 · 4.48 Impact Factor
  • Source
    • "Our data show that the use of normexp background correction with cyclic loess normalization and array weights strongly reduces the number of false-positive up-regulated miRNAs in samples with globally decreased miRNAs for the single-color Affymetrix miRNA microarray platform. This approach also yielded a strong reduction in false-positive up-regulated miRNAs and the detection of the greatest amount of truly down-regulated miRNAs in the analysis of prostate cancer samples where miRNAs were preferentially down-regulated (Ozen et al. 2008; Szczyrba et al. 2010; Wach et al. 2012). Given their relatively low cost compared to other technologies such as RNA sequencing, miRNA microarrays remain a very popular method of characterizing miRNA profiles across samples. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have established that mutations or deletions in microRNA (miRNA) processing enzymes resulting in a global decrease of miRNA expression are frequent across cancers and can be associated with a poorer prognosis. While very popular in miRNA profiling studies, it remains unclear whether miRNA microarrays are suited or not to accurately detecting global miRNA decreases seen in cancers. In this work, we analyzed the miRNA profiles of samples with global miRNA decreases using Affymetrix miRNA microarrays following the inducible genetic deletion of Dicer1. Surprisingly, up to a third of deregulated miRNAs identified upon Dicer1 depletion were found to be up-regulated following standard robust multichip average (RMA) background correction and quantile normalization, indicative of normalization bias. Our comparisons of five preprocess steps performed at the probe level demonstrated that the use of cyclic loess relying on non-miRNA small RNAs present on the Affymetrix platform significantly improved specificity and sensitivity of detection of decreased miRNAs. These findings were validated in samples from patients with prostate cancer, where conjugation of robust normal-exponential background correction with cyclic loess normalization and array weights correctly identified the greatest number of decreased miRNAs, and the lowest amount of false-positive up-regulated miRNAs. These findings highlight the importance of miRNA microarray normalization for the detection of miRNAs that are truly differentially expressed and suggest that the use of cyclic loess based on non-miRNA small RNAs can help to improve the sensitivity and specificity of miRNA profiling in cancer samples with global miRNA decrease.
    RNA 05/2013; 19(7). DOI:10.1261/rna.035055.112 · 4.62 Impact Factor
Show more