HuR Knockdown Changes the Oncogenic Potential of Oral Cancer Cells

• Kakuguchi, Wataru

• Kitamura, Tetsuya

• Kuroshima, Takeshi

• Ishikawa, Makoto

• Kitagawa, Yoshimasa

• Totsuka, Yasunori

• Shindoh, Masanobu

• Higashino, Fumihiro

抄録

HuR binds to AU-rich element (ARE) containing mRNA to protect them from rapid degradation. Here, we show that knockdown of HuR changes the oncogenic properties of oral cancer cells. Oral squamous cell carcinoma cell lines, HSC-3 and Ca9.22, which express HuR protein and cytoplasmic ARE-mRNA more abundantly than normal cells, were subjected to HuR knockdown. In the HuR-knockdown cancer cells, the cytoplasmic expression of c-fos, c-myc, and COX-2 mRNAs was inhibited compared to those in cells that had been transfected with a control siRNA, and the half-lives of these mRNAs were shorter than those of their counterparts in the control cells. HuR-knockdown cells failed to make colonies in soft agar, suggesting that the cells had lost their ability for anchorage-independent cell growth. Additionally, the motile and invasive activities of the cells decreased remarkably by HuR knockdown. Furthermore, the expression of cell cycle-related proteins, such as cyclin A, cyclin B1, cyclin D1, and CDK1, was reduced in the HuR-knockdown cancer cells, and HuR bound to cdk1 mRNA in order to stabilize it. These findings suggest that HuR knockdown changes the features of oral cancer cells, at least in part, by affecting their cell cycle, and shows potential as an effective therapeutic approach.

収録刊行物

• Molecular Cancer Research

  Molecular Cancer Research 8 (4), 520-528, 2010-04

  American Association for Cancer Research

キーワード

• HuR
• knockdown
• AU-rich element
• anchorage-independent cell growth
• cell cycle-related proteins

詳細情報

• CRID: 1050001339005871872
• NII論文ID: 120002834688
• HANDLE: 2115/45096
• ISSN: 15417786
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles
  • KAKEN