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Aberrant expression of microRNAs in bladder cancer

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From Nature Reviews Urology

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Abstract

MicroRNAs (miRNAs), a class of small noncoding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to bladder cancer development, progression and metastasis. Genome-wide miRNA expression signatures have been used to rapidly and precisely identify aberrant miRNA expression in bladder cancer. Based on reports describing miRNA signatures, several downregulated and upregulated miRNAs have been discovered. Examination of the differential expression of miRNAs between clinical bladder cancer and normal bladder tissue has led to the elucidation of 11 miRNA expression signatures. miRNAs downregulated in bladder cancer, such as miR-145, miR-143 and miR125b, are known to be tumour suppressors, whereas upregulated miRNAs, such as miR-183, miR-96, miR17-5p and miR-20a are oncogenic. Several studies have demonstrated the potential of miRNAs for providing prognostic information. miR-145 is the most frequently downregulated miRNA in bladder cancer and has been shown to significantly inhibit proliferation, migration and invasion. Understanding the role of differentially expressed miRNAs, as well as their molecular targets, in bladder cancer will provide an effective and promising strategy for miRNA-based therapeutics for the treatment of bladder cancer.

Key Points

  • Most clinical trials of chemotherapeutics for advanced bladder cancer have shown limited benefits, so new prognostic markers and effective treatment strategies are necessary

  • Examination of the differential expression of microRNAs (miRNAs) between clinical bladder cancer and normal bladder tissue has led to the elucidation of 11 bladder-cancer-specific miRNA expression signatures

  • miRNAs frequently observed in bladder cancer might be the driver molecules for cancer progression

  • Although some miRNAs might be promising prognostic markers, the results are somewhat inconsistent, and measurement of expression levels of miRNAs has not been standardized across studies

  • miRNAs have been shown to be involved in crucial cell mechanisms, such as apoptosis, the cell cycle and epithelial–mesenchymal transition

  • Dysregulation of signalling pathways downstream of miR-145 has been implicated in the progression of bladder cancer

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Figure 1: The microRNA (miRNA) processing pathway.

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Authors and Affiliations

  1. Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan

    Hirofumi Yoshino, Toshihiko Itesako, Takeshi Chiyomaru, Masayuki Nakagawa & Hideki Enokida

  2. Department of Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, 260-8670, Chiba, Japan

    Naohiko Seki

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  1. Hirofumi Yoshino
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H. Yoshino and N. Seki contributed equally to the discussion of content and writing of this article. H. Yoshino, T. Itesako and T. Chiyomaru researched data for the article. H. Enokida contributed to discussion of content. H. Enokida, N. Seki and M. Nakagawa reviewed the manuscript before submission.

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Correspondence to Hideki Enokida.

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Supplementary Table 1

Differentially expressed miRNAs in bladder cancer (DOC 53 kb)

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Yoshino, H., Seki, N., Itesako, T. et al. Aberrant expression of microRNAs in bladder cancer. Nat Rev Urol 10, 396–404 (2013). https://doi.org/10.1038/nrurol.2013.113

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