Open Access

miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer

  • Authors:
    • Shuichi Tatarano
    • Takeshi Chiyomaru
    • Kazumori Kawakami
    • Hideki Enokida
    • Hirofumi Yoshino
    • Hideo Hidaka
    • Takeshi Yamasaki
    • Kazuya Kawahara
    • Kenryu Nishiyama
    • Naohiko Seki
    • Masayuki Nakagawa
  • View Affiliations

  • Published online on: April 20, 2011     https://doi.org/10.3892/ijo.2011.1012
  • Pages: 13-21
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Abstract

Growing evidence suggests that microRNAs (miRNAs) are aberrantly expressed in many human cancers, and that they play significant roles in carcinogenesis and cancer progression. The identification of tumor suppressive miRNAs and their target genes could provide new insights into the mechanism of carcinogenesis. However, the genetic or epigenetic regulations of these miRNAs have not yet been fully elucidated in bladder cancer (BC). Chromosomal alter­ations of cancer cells give us important information for the identification of tumor suppressor genes. Our miRNA array-comparative genomic hybridization (CGH) analysis showed several miRNAs to be candidate tumor suppressors of BC. Our array-CGH analysis revealed that chromosome 4 was lost in all BC cell lines. We selected 19 miRNAs located on chromosome 4 and evaluated their expression levels in cancer cell lines as well as clinical samples. Gain-of-function analysis revealed that miR-218 inhibited BC cell proliferation, migra­tion and invasion. Furthermore, flow cytometry analysis showed that it induced BC cell apoptosis. Genome-wide gene expression analysis showed that it targeted multiple oncogenes in BC. Our study is the first to demonstrate that miR-218 located on chrosomosme 4p15.31 is a tumor suppressive miRNA in BC. The identification of tumor suppressive miRNAs and their target genes on the basis of array-CGH analysis could provide new insights into the mechanisms of BC carcinogenesis.

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July 2011
Volume 39 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tatarano S, Chiyomaru T, Kawakami K, Enokida H, Yoshino H, Hidaka H, Yamasaki T, Kawahara K, Nishiyama K, Seki N, Seki N, et al: miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer. Int J Oncol 39: 13-21, 2011
APA
Tatarano, S., Chiyomaru, T., Kawakami, K., Enokida, H., Yoshino, H., Hidaka, H. ... Nakagawa, M. (2011). miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer. International Journal of Oncology, 39, 13-21. https://doi.org/10.3892/ijo.2011.1012
MLA
Tatarano, S., Chiyomaru, T., Kawakami, K., Enokida, H., Yoshino, H., Hidaka, H., Yamasaki, T., Kawahara, K., Nishiyama, K., Seki, N., Nakagawa, M."miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer". International Journal of Oncology 39.1 (2011): 13-21.
Chicago
Tatarano, S., Chiyomaru, T., Kawakami, K., Enokida, H., Yoshino, H., Hidaka, H., Yamasaki, T., Kawahara, K., Nishiyama, K., Seki, N., Nakagawa, M."miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer". International Journal of Oncology 39, no. 1 (2011): 13-21. https://doi.org/10.3892/ijo.2011.1012