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Article

Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers

  • Authors:
    • Takayuki Muraoka
    • Junichi Soh
    • Shinichi Toyooka
    • Yuho Maki
    • Kazuhiko Shien
    • Masashi Furukawa
    • Tsuyoshi Ueno
    • Norimitsu Tanaka
    • Hiromasa Yamamoto
    • Hiroaki Asano
    • Kazunori Tsukuda
    • Shinichiro Miyoshi
  • View Affiliations / Copyright

    Affiliations: Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama 700-8558, Japan
  • Pages: 185-189
    |
    Published online on: September 3, 2012
       https://doi.org/10.3892/mco.2012.18
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Abstract

MicroRNAs (miRs) contribute to cancer develop­ment and progression by acting as oncogenes and tumor suppressor genes. miR‑9 family members (miR‑9s), including miR‑9‑1, 9‑2 and 9‑3, have been shown to be oncogenically involved through the downregulation of E‑cadherin expression, which promotes the epithelial-mesenchymal transition. Tumor suppressive roles of miR‑9s have also been reported to silence miR‑9 through methylation, which is associated with an shortened overall survival (OS) period in several types of cancer. In this study, the impact of miR‑9s methylation on non‑small cell lung cancers (NSCLC) was investigated. In total, 293 resected NSCLC samples were examined and the miR‑9s methylation status was determined using a combined bisulfite restriction analysis. miR-9 expression was analyzed by in situ hybridization. Methylation of miR-9-1, 9-2 and 9-3 was present in 20 (7%), 33 (11%) and 34 (12%) of the cases, respectively. Methylation of any miR-9s (miR‑9s methylation) was observed in 76 of the cases (26%), and miR‑9 expression was silenced in cases with miR‑9s methylation. Logistic regression analysis demonstrated that male gender [odds ratio (OR), 2.0; 95% confidence interval (95% CI), 1.1‑3.6; P=0.01] and pathologically negative lymph node metastasis (OR, 4.8; 95% CI, 1.4‑17.2; P=0.002) were independent relative factors for miR‑9s methylation. Additionally, miR‑9s methylation [hazard ratio (HR), 4.2; 95% CI, 1.2-27.0; P=0.026] and early pathological stage (HR, 8.3; 95% CI, 2.1-28.6; P=0.004) were found to be independent predictive factors for prolonged OS time by the Cox proportional hazard test. miR‑9s methylation which induces expression silencing is common in NSCLC cases without lymph nodal metastasis, suggesting that miR‑9s are oncogenically involved in NSCLC carcinogenesis through the promotion of tumor metastasis.
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Copy and paste a formatted citation
Spandidos Publications style
Muraoka T, Soh J, Toyooka S, Maki Y, Shien K, Furukawa M, Ueno T, Tanaka N, Yamamoto H, Asano H, Asano H, et al: Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers. Mol Clin Oncol 1: 185-189, 2013.
APA
Muraoka, T., Soh, J., Toyooka, S., Maki, Y., Shien, K., Furukawa, M. ... Miyoshi, S. (2013). Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers. Molecular and Clinical Oncology, 1, 185-189. https://doi.org/10.3892/mco.2012.18
MLA
Muraoka, T., Soh, J., Toyooka, S., Maki, Y., Shien, K., Furukawa, M., Ueno, T., Tanaka, N., Yamamoto, H., Asano, H., Tsukuda, K., Miyoshi, S."Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers". Molecular and Clinical Oncology 1.1 (2013): 185-189.
Chicago
Muraoka, T., Soh, J., Toyooka, S., Maki, Y., Shien, K., Furukawa, M., Ueno, T., Tanaka, N., Yamamoto, H., Asano, H., Tsukuda, K., Miyoshi, S."Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers". Molecular and Clinical Oncology 1, no. 1 (2013): 185-189. https://doi.org/10.3892/mco.2012.18
Copy and paste a formatted citation
x
Spandidos Publications style
Muraoka T, Soh J, Toyooka S, Maki Y, Shien K, Furukawa M, Ueno T, Tanaka N, Yamamoto H, Asano H, Asano H, et al: Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers. Mol Clin Oncol 1: 185-189, 2013.
APA
Muraoka, T., Soh, J., Toyooka, S., Maki, Y., Shien, K., Furukawa, M. ... Miyoshi, S. (2013). Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers. Molecular and Clinical Oncology, 1, 185-189. https://doi.org/10.3892/mco.2012.18
MLA
Muraoka, T., Soh, J., Toyooka, S., Maki, Y., Shien, K., Furukawa, M., Ueno, T., Tanaka, N., Yamamoto, H., Asano, H., Tsukuda, K., Miyoshi, S."Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers". Molecular and Clinical Oncology 1.1 (2013): 185-189.
Chicago
Muraoka, T., Soh, J., Toyooka, S., Maki, Y., Shien, K., Furukawa, M., Ueno, T., Tanaka, N., Yamamoto, H., Asano, H., Tsukuda, K., Miyoshi, S."Impact of aberrant methylation of microRNA-9 family members on non-small cell lung cancers". Molecular and Clinical Oncology 1, no. 1 (2013): 185-189. https://doi.org/10.3892/mco.2012.18
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