Lin Zhipeng, Hu Baoying, Ni Wenkai, Mao Xiaofei, Zhou Huiling, Lv Jiale, Yin Bihui, Shen Zhongyi, Wu Miaomiao, Ding Wensen, Xiao Mingbing, Ni Runzhou
Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
Basic Medical Research Centre, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Tumour Biol. 2016 Dec;37:16305–16315. doi: 10.1007/s13277-016-5424-0. Epub 2016 Nov 10.
BCCIP was originally identified as a BRCA2- and CDKN1A- (Cip1/waf1/p21) interacting protein, also known as BCCIP. It has been reported to express in various types of cancers, including colorectal cancer (CRC), astrocytic brain tumors, and glioblastomas. However, the relationship between BCCIP expression and clinicopathological features of hepatocellular carcinoma (HCC) remains to be determined. Herein, we demonstrated that BCCIP was downregulated in clinical HCC tissues; its level was inversely correlated with multiple clinicopathological factors, such as tumor grade, tumor size, and Ki67 expression. Cox regression analysis of tumor samples revealed that BCCIP expression status was an independent prognostic factor for HCC patients' poor survival. Our study also indicated that BCCIP shutdown reduces p21 expression and accelerates G1 to S progression of LO2 hepatocytes significantly. Moreover, there is an interaction between BCCIP and p53 in hepatic L02 cells, and the downregulation of p21 expression by BCCIP is in a p53-dependent way. These findings revealed that BCCIP may play a significant role for the determination of HCC progression through its role in regulating cell growth. Thus, our results suggest that BCCIP is of potential interest for prognostic marker and therapeutic target of HCC.
BCCIP最初被鉴定为一种与BRCA2和CDKN1A（Cip1/waf1/p21）相互作用的蛋白质，也被称为BCCIP。据报道，它在多种类型的癌症中表达，包括结直肠癌（CRC）、星形细胞瘤性脑肿瘤和胶质母细胞瘤。然而，BCCIP表达与肝细胞癌（HCC）临床病理特征之间的关系仍有待确定。在此，我们证明了BCCIP在临床HCC组织中表达下调；其水平与多种临床病理因素呈负相关，如肿瘤分级、肿瘤大小和Ki67表达。对肿瘤样本的Cox回归分析显示，BCCIP表达状态是HCC患者生存不良的独立预后因素。我们的研究还表明，BCCIP的缺失会降低p21表达，并显著加速LO2肝细胞从G1期到S期的进程。此外，在肝L02细胞中，BCCIP与p53之间存在相互作用，且BCCIP对p21表达的下调是以p53依赖的方式进行的。这些发现揭示了BCCIP可能通过其在调节细胞生长中的作用，在HCC进展的决定中发挥重要作用。因此，我们的结果表明，BCCIP对于HCC的预后标志物和治疗靶点具有潜在的研究价值。
