SNF5 is Involved in Suppression of Hepatocellular Carcinoma Progression via TGF‐Beta 1 Signaling
SNF5 is Involved in Suppression of Hepatocellular Carcinoma Progression via TGF‐Beta 1 Signaling
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DOI：
10.1002/ar.23357
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Hongmiao Sun;Xinping Zhong;Chunyu Wang;Shengli Wang;Lin Lin-Lin;Renlong Zou;Yi Wu;Ning Sun;Ge S
中科院分区：
文献类型：
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作者：
Hongmiao Sun;Xinping Zhong;Chunyu Wang;Shengli Wang;Lin Lin-Lin;Renlong Zou;Yi Wu;Ning Sun;Ge S
SNF 5（SMARCB 1/INI 1/BAF 47）是SWI/SNF复合物的核心亚基，具有调节细胞增殖和凋亡的作用。遗传学证据表明SNF 5参与肿瘤抑制。然而，SNF 5在肝细胞癌（HCC）进展中的详细生物学功能和潜在机制仍不清楚。在这里，已经证明了与邻近的非癌组织相比，HCC组织中SNF 5表达降低。重要的是，研究结果表明，SNF 5表达减少与HCC患者的总体生存率较低有很强的相关性。数据表明，SNF 5的敲低显著促进Hep 3B和HCCLM 3细胞系中的细胞生长和迁移。有趣的是，研究发现SNF 5抑制转化生长因子-β1（TGF-β1）的表达，并且SNF 5 mRNA表达与HCC组织中的TGF-β1呈负相关。此外，SNF 5的缺失减弱了HCC细胞对索拉非尼的敏感性。因此，SNF 5可能参与了肝癌的抑制作用，其表达水平的降低与肝癌的分化程度和预后相关，提示SNF 5可能是一个重要的肝癌预后生物标志物和有希望的治疗靶点。Anat Rec，299：869-877，2016。© 2016 Wiley Periodicals，Inc.
SNF5 (SMARCB1/INI1/BAF47), a core subunit of SWI/SNF complex, has been reported to modulate cell proliferation and apoptosis. Genetic evidence has suggested that SNF5 participates in tumor suppression. However, the detailed biological function and underlying mechanisms of SNF5 in hepatocellular carcinoma (HCC) progression remain unclear. Here, SNF5 expression reduction in HCC tissues compared with the adjacent non‐cancerous tissues has been demonstrated. Importantly, the results showed that reduced SNF5 expression has a strong correlation with worse overall survival of HCC patients. The data demonstrated that knockdown of SNF5 significantly promoted cell growth and migration in Hep3B and HCCLM3 cell lines. Interestingly, it was found that SNF5 suppressed transforming growth factor‐β1 (TGF‐β1) expression, and SNF5 mRNA expression was negatively correlated with TGF‐β1 in HCC tissues. Furthermore, depletion of SNF5 attenuated the sensitivity of HCC cells to sorafenib. Thus, the data suggested that SNF5 may participate in HCC suppression, and reduced expression of SNF5 correlates with the poor differentiation and prognosis of HCC, indicating that SNF5 might be an important prognostic biomarker and promising therapeutic target for HCC. Anat Rec, 299:869–877, 2016. © 2016 Wiley Periodicals, Inc.