Glutathione S-transferase P1 (GSTP1) suppresses cell apoptosis and its regulation by miR-133α in head and neck squamous cell carcinoma (HNSCC)

  • Authors:
    • Muradil Mutallip
    • Nijiro Nohata
    • Toyoyuki Hanazawa
    • Naoko Kikkawa
    • Shigetoshi Horiguchi
    • Lisa Fujimura
    • Kazumori Kawakami
    • Takeshi Chiyomaru
    • Hideki Enokida
    • Masayuki Nakagawa
    • Yoshitaka Okamoto
    • Naohiko Seki
  • Corresponding author:
  • View Affiliations

  • Published online on: Wednesday, December 22, 2010
  • Pages: 345-352 DOI: 10.3892/ijmm.2010.589

Abstract

The glutathione S-transferase P1 (GSTP1) protein plays several critical roles in both normal and neoplastic cells, including phase II xenobiotic metabolism, stress responses, signaling and apoptosis. Overexpression of GSTP1 has been observed in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the role of GSTP1 in HNSCC is not well understood. We investigated the role of GSTP1 in two HNSCC cell lines, HSC3 and SAS. Silencing of GSTP1 revealed that cancer cell proliferation was significantly decreased in both cell lines. In addition, the frequency of apoptotic cells increased following si-GSTP1 transfection of HSC3 and SAS cell lines. Growing evidence suggests that microRNAs (miRNAs) negatively regulate gene expression and can function as oncogenes or tumor suppressors in human cancer. Based on the results of web-based searches, miR-133α is a candidate miRNA targeting GSTP1. Down-regulation of miR-133α has been reported in many types of human cancer, including HNSCC. Transient transfection of miR-133α repressed the expression of GSTP1 at both the mRNA and protein levels. The signal from a luciferase reporter was significantly decreased at one miR-133α target site at the 3'UTR of GSTP1, suggesting that miR-133α directly regulates GSTP1. Our data indicate that GSTP1 may have an oncogenic function and may be regulated by miR-133α, a tumor suppressive miRNA in HNSCC. The identification of a novel oncogenic pathway could provide new insights into potential mechanisms of HNSCC carcinogenesis.
Journal Cover

March 2011
Volume 27 Issue 3

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

2013 Impact Factor: 1.88
2014 I.F. (Expected) ≥ 2.327 Ranked #27/122 Medicine Research and Experimental
(total number of cites)

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APA
Mutallip, M., Nohata, N., Hanazawa, T., Kikkawa, N., Horiguchi, S., Fujimura, L. ... Seki, N. (2011). Glutathione S-transferase P1 (GSTP1) suppresses cell apoptosis and its regulation by miR-133α in head and neck squamous cell carcinoma (HNSCC). International Journal of Molecular Medicine, 27, 345-352. http://dx.doi.org/10.3892/ijmm.2010.589
MLA
Mutallip, M., Nohata, N., Hanazawa, T., Kikkawa, N., Horiguchi, S., Fujimura, L., Kawakami, K., Chiyomaru, T., Enokida, H., Nakagawa, M., Okamoto, Y., Seki, N."Glutathione S-transferase P1 (GSTP1) suppresses cell apoptosis and its regulation by miR-133α in head and neck squamous cell carcinoma (HNSCC)". International Journal of Molecular Medicine 27.3 (2011): 345-352.
Chicago
Mutallip, M., Nohata, N., Hanazawa, T., Kikkawa, N., Horiguchi, S., Fujimura, L., Kawakami, K., Chiyomaru, T., Enokida, H., Nakagawa, M., Okamoto, Y., Seki, N."Glutathione S-transferase P1 (GSTP1) suppresses cell apoptosis and its regulation by miR-133α in head and neck squamous cell carcinoma (HNSCC)". International Journal of Molecular Medicine 27, no. 3 (2011): 345-352. http://dx.doi.org/10.3892/ijmm.2010.589