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首页> 外文期刊>International journal of oncology >Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines
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Genetic screen identifies suppressor of morphogenesis in genitalia-1 (SMG-1) as a modulator of sorafenib resistance in hepatocellular carcinoma cell lines

机译：遗传筛查确定生殖器1（SMG-1）中的形态发生抑制子是肝细胞癌细胞系中索拉非尼耐药的调节剂

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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.
机译：肝细胞癌（HCC）是一种侵袭性恶性肿瘤，预后较差，分子病因异常复杂。此外，迄今为止，常规疗法仅取得了有限的成功。最近开发的口服多激酶抑制剂索拉非尼已被用于改善HCC患者的生存率，但是，随访研究显示癌症的复发率很高。因此，迫切需要鉴定涉及索拉非尼耐药性的基因。 RNA干扰（RNAi）是执行功能丧失的基因筛选的强大工具，可以促进细胞信号传导途径组分的鉴定。这项研究描述了在HCC细胞系中使用RNAi进行无偏基因组筛选的结果，以阐明与索拉非尼无反应性或抗性相关的基因。全基因组的体外RNA干扰筛选揭示了生殖器1（SMG-1）中的形态发生抑制子作为索拉非尼耐药性的决定因素。在研究的HCC细胞系中，SMG-1的抑制作用降低了索拉非尼的敏感性。癌性和非癌性区域的免疫组织化学比较显示，HCC的非肿瘤性肝细胞区域有很强的染色。 SMG-1可能需要作为逆转索拉非尼耐药的药物进行调查。

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