SREBP-1 has a prognostic role and contributes to invasion and metastasis in human hepatocellular carcinoma.

SREBP-1 has a prognostic role and contributes to invasion and metastasis in human hepatocellular carcinoma.
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SREBP-1 在人肝细胞癌中具有预后作用并有助于侵袭和转移

DOI:
10.3390/ijms15057124
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发表时间:
2014-04-25
影响因子:
5.6
通讯作者:
Liu Q
Liu Q
中科院分区:
生物学2区
文献类型:
--
作者:
Li C;Yang W;Zhang J;Zheng X;Yao Y;Tu K;Liu Q

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固醇调节元件结合蛋白1(SREBP-1)是一种参与脂质合成的核转录因子。近年来的研究主要集中在其在肿瘤细胞增殖和凋亡中的作用,但其在细胞迁移和侵袭中的作用,特别是在肝细胞癌(HCC)中的作用尚不清楚。在本研究中,我们发现SREBP-1在肝癌组织中的表达显著高于癌旁组织(p < 0.05)。SREBP-1在肿瘤体积大、组织学分级高、TNM分期高的患者中表达明显增高(p < 0.05)。SREBP-1阳性表达与肝癌患者3年总生存率和无瘤生存率相关(p < 0.05)。此外,SREBP-1是预测HCC患者3年总生存率和无病生存率的独立因素(p < 0.05)。体外研究表明,下调SREBP-1可抑制HepG 2和MHCC 97 L细胞的增殖并诱导其凋亡(p < 0.05)。此外,伤口愈合和transwell测定显示SREBP-1敲低显著抑制HepG 2和MHCC 97 L细胞中的细胞迁移和侵袭(p < 0.05)。这些结果表明,SREBP-1可能作为HCC的预后标志物,并可能通过促进细胞生长和转移促进肿瘤进展。
Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC), is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05). SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM) stage (p < 0.05). The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05). Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05). In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05). Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05). These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis.
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