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

Nam,Soon  Woo; Park,Ki  Cheol; Yang,Keum  Jin; Lee,Byoungchun; Kim,Sung-Woo

doi:10.3892/ijo.2014.2540

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
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Affiliations: Hepatobiliary Unit, Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, Medical School of the Catholic University of Korea, Incheon, Republic of Korea, Clinical Medicine Research Institute, Daejeon St. Mary's Hospital, Daejeon, Republic of Korea, Southern Alberta Cancer Research Institute, Departments of Biochemistry and Molecular Biology, University of Calgary, AB, Canada
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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