Yin Guozhi, Liu Zhikui, Wang Yufeng, Dou Changwei, Li Chao, Yang Wei, Yao Yingmin, Liu Qingguang, Tu Kangsheng
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, No.277 Yanta West Road, Xi'an, 710061, China.
BMC Cancer. 2016 Feb 15;16:103. doi: 10.1186/s12885-016-2154-z.
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.
E-钙黏蛋白的失调被认为是肝细胞癌（HCC）转移的主要原因。BCL6共抑制因子样1（BCORL1）是一种转录共抑制因子，有助于抑制E-钙黏蛋白。然而，BCORL1的临床意义及其在HCC转移中的作用仍不清楚。
通过蛋白质免疫印迹法检测HCC与配对的癌旁组织、HCC细胞系和正常肝细胞系之间差异表达的BCORL1。利用小干扰RNA（siRNAs）或慢病毒介导的载体改变BCORL1的表达。进行Transwell实验以确定HCC细胞的侵袭和迁移能力。
在HCC标本和细胞系中检测到BCORL1蛋白表达增加。临床关联分析表明，在具有多个肿瘤结节、静脉浸润和晚期TNM肿瘤分期的HCC患者中，BCORL1蛋白表达水平显著更高。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）缩短。多变量Cox回归分析显示，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显著促进HCC细胞的迁移和侵袭。此外，在HCC组织中观察到BCORL1与E-钙黏蛋白表达呈负相关。BCORL1反向调节E-钙黏蛋白的丰度，随后促进HCC细胞的上皮-间质转化（EMT）。值得注意的是，E-钙黏蛋白沉默消除了BCORL1敲低对HCC细胞的影响。
BCORL1可能是一种新的预后因子，并通过抑制E-钙黏蛋白诱导的EMT促进HCC细胞的迁移和侵袭。
