Significance of polypyrimidine tract-binding protein 1 expression in colorectal cancer

Hidekazu Takahashi, Junichi Nishimura, Yoshinori Kagawa, Yoshihiro Kano, Yusuke Takahashi, Xin Wu, Masayuki Hiraki, Atsushi Hamabe, Masamitsu Konno, Naotsugu Haraguchi, Ichiro Takemasa, Tsunekazu Mizushima, Masaru Ishii, Koshi Mimori, Hideshi Ishii, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto

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28 Citations (Scopus)

Abstract

Polypyrimidine tract-binding protein (PTBP1) is an RNAbinding protein with various molecular functions related to RNA metabolism and amajor repressive regulator of alternative splicing, causing exon skipping in numerous alternatively spliced pre-mRNAs. Here, we have investigated the role of PTBP1 in colorectal cancer. PTBP1 expression levels were significantly overexpressed in cancerous tissues compared with corresponding normal mucosal tissues. We also observed that PTBP1 expression levels, c-MYC expression levels, and PKM2: PKM1 ratio were positively correlated in colorectal cancer specimens. Moreover, PTBP1 expression levels were positively correlated to poor prognosis and lymph node metastasis. In analyses of colorectal cancer cells using siRNA for PTBP1, we observed that PTBP1 affects cell invasion, which was partially correlated to CD44 splicing, and this correlation was also confirmed in clinical samples. PTBP1 expression also affected anchorage-independent growth in colorectal cancer cell lines. PTBP1 expression also affected cell proliferation. Using timelapse imaging analysis, PTBP1 was implicated in prolonged G2-M phase in HCT116 cells. As for the mechanism of prolonged G2-M phase in HCT116 siPTBP1 cells, Western blotting revealed that PTBP1 expression level was correlated to CDK11p58 expression level, which was reported to play an important role on progression to complete mitosis. These findings indicated that PTBP1 is a potential therapeutic target for colorectal cancer.

Original languageEnglish
Pages (from-to)1705-1716
Number of pages12
JournalMolecular cancer therapeutics
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 1 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Takahashi, H., Nishimura, J., Kagawa, Y., Kano, Y., Takahashi, Y., Wu, X., Hiraki, M., Hamabe, A., Konno, M., Haraguchi, N., Takemasa, I., Mizushima, T., Ishii, M., Mimori, K., Ishii, H., Doki, Y., Mori, M., & Yamamoto, H. (2015). Significance of polypyrimidine tract-binding protein 1 expression in colorectal cancer. Molecular cancer therapeutics, 14(7), 1705-1716. https://doi.org/10.1158/1535-7163.MCT-14-0142