Anti-oncogenic activities of cyclin D1b siRNA on human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and invasiveness

  • Authors:
    • Chul Jang Kim
    • Tokio Terado
    • Yukihiro Tambe
    • Ken-Ichi Mukaisho
    • Hiroyuki Sugihara
    • Akihiro Kawauchi
    • Hirokazu Inoue
  • View Affiliations

  • Published online on: November 7, 2017     https://doi.org/10.3892/ijo.2017.4194
  • Pages:231-240
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Abstract

The human cyclin D1 gene generates two major isoforms, cyclin D1a and cyclin D1b, by alternative splicing. Although cyclin D1b mRNA is hardly expressed in normal human tissues, it is detected in approximately 60% of human bladder cancer tissues and cell lines. In the present study, to assess the therapeutic ability of cyclin D1b siRNA, we investigated the anti-oncogenic effects of cyclin D1b siRNA on human bladder cancer cell lines, SBT31A and T24, which express cyclin D1b mRNA. Knockdown of cyclin D1b by specific siRNA significantly suppressed cell proliferation, in vitro cell invasiveness and three-dimensional (3D) spheroid formation in these cell lines. Cell cycle analyses revealed that cyclin D1b siRNA inhibited G1-S transition in T24 cells. The increase in the sub-G1 fraction, morphological aberrant nuclei with nuclear fragmentation and caspase-3 activity in SBA31A cells treated with cyclin D1b siRNA showed that cyclin D1b siRNA induced apoptosis. In T24 cells, knockdown of cyclin D1b suppressed the expression of the stem cell marker CD44. Knockdown of cyclin D1b or CD44 suppressed the invasiveness under 3D spheroid culture conditions and expression of N-cadherin. Tumor growth of SBT31A cells in nude mice was significantly inhibited by cyclin D1b siRNA. Taken together, these results indicate that knockdown of cyclin D1b suppresses the malignant phenotypes of human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and epithelial-mesenchymal transition. Applying cyclin D1b siRNA will be a novel therapy for cyclin D1b-expressing bladder cancers.

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January 2018
Volume 52 Issue 1

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

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APA
Kim, C.J., Terado, T., Tambe, Y., Mukaisho, K., Sugihara, H., Kawauchi, A., & Inoue, H. (2018). Anti-oncogenic activities of cyclin D1b siRNA on human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and invasiveness. International Journal of Oncology, 52, 231-240. https://doi.org/10.3892/ijo.2017.4194
MLA
Kim, C. J., Terado, T., Tambe, Y., Mukaisho, K., Sugihara, H., Kawauchi, A., Inoue, H."Anti-oncogenic activities of cyclin D1b siRNA on human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and invasiveness". International Journal of Oncology 52.1 (2018): 231-240.
Chicago
Kim, C. J., Terado, T., Tambe, Y., Mukaisho, K., Sugihara, H., Kawauchi, A., Inoue, H."Anti-oncogenic activities of cyclin D1b siRNA on human bladder cancer cells via induction of apoptosis and suppression of cancer cell stemness and invasiveness". International Journal of Oncology 52, no. 1 (2018): 231-240. https://doi.org/10.3892/ijo.2017.4194