CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer

  • Authors:
    • Mitsugi Matsumoto
    • Kazumori Kawakami
    • Hideki Enokida
    • Kazuki Toki
    • Ryoichiro Matsuda
    • Takeshi Chiyomaru
    • Kenryu Nishiyama
    • Kazuya Kawahara
    • Naohiko Seki
    • Masayuki Nakagawa
  • View Affiliations

  • Published online on: August 1, 2010     https://doi.org/10.3892/ijmm_00000458
  • Pages: 241-247
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Abstract

We previously reported a simple technique that combines microarray data from clinical bladder cancer (BC) specimens with those from a BC cell line (BOY) treated with a pharmacologic demethylating agent (5-aza-dC). We focused on the human four-and-a-half LIM domains 1 (FHL1) gene which was selected on the basis of previous microarray data analysis. Because LIM domains provide protein-protein binding interfaces, FHL genes play an important role in cellular events, such as focal adhesion and differentiation, by interacting with the target protein as either a repressor or activator. We hypothesized that inactivation of the FHL1 gene through CpG methylation contributes to cell viability including migration and invasion activity of human BC. After 5-aza-dC treatment, the expression levels of FHL1 mRNA transcript markedly increased in all cell lines tested, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR). The methylation index of FHL1 in our samples was significantly higher in 70 BC specimens than in 10 normal bladder epithelium (NBE) specimens (63.9±25.5 and 0.3±0.2, respectively; p=0.0066). Conversely, FHL1 mRNA expression was significantly lower in the BC specimens than in the NBE ones (0.331±0.12 and 2.498±0.61, respectively; p=0.0011). In addition, significant inhibitions of wound healing (45.78±6.2, and 100±0, respectively; p=0.009) and of cell invasion (18.5±2.3 and 95.2±2.4, respectively; p=0.02) were observed in stable FHL1-transfected cells than in the control BC cells. In conclusion, we found that the mechanism of FHL1 down-regulation in BC is through CpG hypermethylation of the promoter region. FHL1 gene inactivation by CpG hypermethylation may thus contribute to migration and invasion activity of BC.

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August 2010
Volume 26 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Matsumoto, M., Kawakami, K., Enokida, H., Toki, K., Matsuda, R., Chiyomaru, T. ... Nakagawa, M. (2010). CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer. International Journal of Molecular Medicine, 26, 241-247. https://doi.org/10.3892/ijmm_00000458
MLA
Matsumoto, M., Kawakami, K., Enokida, H., Toki, K., Matsuda, R., Chiyomaru, T., Nishiyama, K., Kawahara, K., Seki, N., Nakagawa, M."CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer". International Journal of Molecular Medicine 26.2 (2010): 241-247.
Chicago
Matsumoto, M., Kawakami, K., Enokida, H., Toki, K., Matsuda, R., Chiyomaru, T., Nishiyama, K., Kawahara, K., Seki, N., Nakagawa, M."CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer". International Journal of Molecular Medicine 26, no. 2 (2010): 241-247. https://doi.org/10.3892/ijmm_00000458