BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.
BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.
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BCORL1 是一种独立的预后标志物，有助于人肝细胞癌的细胞迁移和侵袭。
DOI：
10.1186/s12885-016-2154-z
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发表时间：
2016-02-15
期刊：
影响因子：
3.8
通讯作者：
Tu K
中科院分区：
文献类型：
--
作者：
Yin G;Liu Z;Wang Y;Dou C;Li C;Yang W;Yao Y;Liu Q;Tu K
E-钙粘蛋白的失调被认为是肝细胞癌（HCC）转移的主要原因。 BCL6 辅助阻遏物样 1 (BCORL1) 是一种转录辅助阻遏物，有助于抑制 E-钙粘蛋白。然而，BCORL1的临床意义及其在HCC转移中的作用仍不清楚。通过Western blot检测HCC与匹配的癌旁组织、HCC细胞系和正常肝细胞系之间差异表达的BCORL1。 BCORL1 的表达被 siRNA 或慢病毒介导的载体改变。进行 Transwell 测定以确定 HCC 细胞侵袭和迁移。在 HCC 标本和细胞系中检测到 BCORL1 蛋白表达增加。临床关联分析显示，BCORL1蛋白在肿瘤淋巴结多、静脉浸润、TNM肿瘤分期晚期的HCC患者中表达水平显着升高。生存分析表明，BCORL1 蛋白的高表达导致 HCC 患者的总生存期 (OS) 和无复发生存期 (RFS) 较短。多变量Cox回归分析揭示BCORL1表达是预测HCC患者生存的独立预后标志物。我们的体外研究表明，BCORL1 显着促进 HCC 细胞迁移和侵袭。另外，在 HCC 组织中观察到 BCORL1 和 E-钙粘蛋白表达之间呈负相关。 BCORL1 反向调节 E-钙粘蛋白丰度，随后促进 HCC 细胞中的上皮间质转化 (EMT)。值得注意的是，E-钙粘蛋白沉默消除了 BCORL1 敲低对 HCC 细胞的影响。 BCORL1 可能是一种新的预后因素，并通过 E-钙粘蛋白抑制诱导 HCC 中的 EMT 促进细胞迁移和侵袭。本文的在线版本 (doi:10.1186/s12885-016-2154-z) 包含补充材料，可供授权用户使用。
The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC. The online version of this article (doi:10.1186/s12885-016-2154-z) contains supplementary material, which is available to authorized users.