Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines

  • Authors:
    • Soon Woo Nam
    • Ki Cheol Park
    • Keum Jin Yang
    • Byoungchun Lee
    • Sung-Woo Kim
  • View Affiliations

  • Published online on: July 10, 2014     https://doi.org/10.3892/ijo.2014.2540
  • Pages: 1450-1456
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Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis and a very complex dysregulated molecular etiology. Furthermore, conventional therapy thus far has had only limited success. A recently developed oral multikinase inhibitor, sorafenib, has been used to improve survival in HCC patients, however, follow‑up studies have revealed a high rate of cancer recurrence. Therefore, identification of genes involved in sorafenib resistance is urgently required. RNA interference (RNAi) is a powerful tool for performing loss-of-function genetic screens and can facilitate the identification of components of the cellular signaling pathway. This study describes the results of an unbiased genomic screening using RNAi in an HCC cell line to elucidate genes related to sorafenib non-responsiveness or resistance. A genome-wide in vitro RNA interference screen revealed the role of suppressor of morphogenesis in genitalia-1 (SMG-1) as a determinant of sorafenib resistance. The inhibition of SMG-1 reduced sorafenib sensitivity in the studied HCC cell lines. An immunohistochemical comparison of cancerous and non‑cancerous regions showed strong staining in the non‑neoplastic hepatocyte regions of HCC. SMG-1 may warrant investigation as an agent to reverse sorafenib resistance.
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October 2014
Volume 45 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Nam, S.W., Park, K.C., Yang, K.J., Lee, B., & Kim, S. (2014). Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines. International Journal of Oncology, 45, 1450-1456. https://doi.org/10.3892/ijo.2014.2540
MLA
Nam, S. W., Park, K. C., Yang, K. J., Lee, B., Kim, S."Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines". International Journal of Oncology 45.4 (2014): 1450-1456.
Chicago
Nam, S. W., Park, K. C., Yang, K. J., Lee, B., Kim, S."Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines". International Journal of Oncology 45, no. 4 (2014): 1450-1456. https://doi.org/10.3892/ijo.2014.2540