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Article

microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma

  • Authors:
    • Naoko Kikkawa
    • Takashi Kinoshita
    • Nijiro Nohata
    • Toyoyuki Hanazawa
    • Noriko Yamamoto
    • Ichiro Fukumoto
    • Takeshi Chiyomaru
    • Hideki Enokida
    • Masayuki Nakagawa
    • Yoshitaka Okamoto
    • Naohiko Seki
  • View Affiliations / Copyright

    Affiliations: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan, Department of Urology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
  • Pages: 2085-2092
    |
    Published online on: March 19, 2014
       https://doi.org/10.3892/ijo.2014.2349
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Abstract

Our recent study of the microRNA (miRNA) expression signature of hypopharyngeal squamous cell carcinoma (HSCC) revealed that microRNA-504 (miR-504) is significantly downregulated in HSCC tissues, suggesting that this miRNA is a candidate tumor suppressor. However, several previous reports indicated that miR-504 has an oncogenic function through targeting TP53. The aim of this study was to investigate the functional significance of miR-504 in cancer cells and to identify novel targets regulated by this miRNA in HSCC cells. First, we confirmed the downregulation of miR-504 in HSCC clinical specimens (P<0.0001) by qPCR. Using two sources of miR-504 to restore function, we observed significant inhibition of cancer cell proliferation in head and neck SCC (HNSCC) cell lines (FaDu, SAS and HSC3) and HCT116 colon carcinoma cells (p53+/+ and p53-/-). In HNSCC cells, induction of cell cycle arrest was observed by miR-504 transfection. To identify the molecular targets of miR-504, we performed gene expression analysis of miR-504 transfectants and in silico database analyses. Our data showed that cell cycle-related genes (RB1, CDK6, CDC23 and CCND1) were candidate target genes of miR-504. In HSCC clinical specimens, the expression of cyclin-dependent kinase 6 (CDK6) was significantly higher in cancer tissues compared to non-cancer tissues (P=0.0004). A significant inverse correlation between CDK6 and miR-504 expression was found (r=-0.43, P=0.0039). Expression of miR-504 inhibited CDK6 expression in HNSCC cells. Loss of tumor-suppressive miR-504 enhanced HSCC cell proliferation through targeting CDK6. The identification of novel tumor-suppressive miR-504-mediated molecular pathways and targets provide new insights into HSCC oncogenesis.
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Copy and paste a formatted citation
Spandidos Publications style
Kikkawa N, Kinoshita T, Nohata N, Hanazawa T, Yamamoto N, Fukumoto I, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Okamoto Y, et al: microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. Int J Oncol 44: 2085-2092, 2014.
APA
Kikkawa, N., Kinoshita, T., Nohata, N., Hanazawa, T., Yamamoto, N., Fukumoto, I. ... Seki, N. (2014). microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. International Journal of Oncology, 44, 2085-2092. https://doi.org/10.3892/ijo.2014.2349
MLA
Kikkawa, N., Kinoshita, T., Nohata, N., Hanazawa, T., Yamamoto, N., Fukumoto, I., Chiyomaru, T., Enokida, H., Nakagawa, M., Okamoto, Y., Seki, N."microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma". International Journal of Oncology 44.6 (2014): 2085-2092.
Chicago
Kikkawa, N., Kinoshita, T., Nohata, N., Hanazawa, T., Yamamoto, N., Fukumoto, I., Chiyomaru, T., Enokida, H., Nakagawa, M., Okamoto, Y., Seki, N."microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma". International Journal of Oncology 44, no. 6 (2014): 2085-2092. https://doi.org/10.3892/ijo.2014.2349
Copy and paste a formatted citation
x
Spandidos Publications style
Kikkawa N, Kinoshita T, Nohata N, Hanazawa T, Yamamoto N, Fukumoto I, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Okamoto Y, et al: microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. Int J Oncol 44: 2085-2092, 2014.
APA
Kikkawa, N., Kinoshita, T., Nohata, N., Hanazawa, T., Yamamoto, N., Fukumoto, I. ... Seki, N. (2014). microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma. International Journal of Oncology, 44, 2085-2092. https://doi.org/10.3892/ijo.2014.2349
MLA
Kikkawa, N., Kinoshita, T., Nohata, N., Hanazawa, T., Yamamoto, N., Fukumoto, I., Chiyomaru, T., Enokida, H., Nakagawa, M., Okamoto, Y., Seki, N."microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma". International Journal of Oncology 44.6 (2014): 2085-2092.
Chicago
Kikkawa, N., Kinoshita, T., Nohata, N., Hanazawa, T., Yamamoto, N., Fukumoto, I., Chiyomaru, T., Enokida, H., Nakagawa, M., Okamoto, Y., Seki, N."microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma". International Journal of Oncology 44, no. 6 (2014): 2085-2092. https://doi.org/10.3892/ijo.2014.2349
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