DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway
DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway
复制标题
DEPDC1通过调节CCL20/CCR6信号通路驱动肝癌细胞增殖、侵袭和血管生成
DOI：
10.3892/or.2019.7221
复制
发表时间：
2019-09-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Ziwei
中科院分区：
文献类型：
--
作者：
Guo, Wubin;Li, Hui;Wang, Ziwei
DEP domain containing 1（DEPDC 1）是肝细胞癌（HCC）的癌基因。然而，DEPDC 1的潜在机制在很大程度上仍然未知。目前的研究表明，DEPDC 1敲低抑制肝癌细胞增殖，集落形成和体外侵袭，并抑制肝癌异种移植物的生长在体内。此外，DEPDC 1过表达促进HCC细胞增殖、集落形成和侵袭。基因芯片、逆转录定量PCR和蛋白质印迹分析结果表明，DEPDC 1基因敲除可显著抑制Huh-7细胞趋化因子（C-C motif）配体20（CCL 20）和趋化因子（C-C motif）受体6（CCR 6）的表达。此外，CCL 20和CCR 6在肝癌组织和细胞系中表达上调，且与DEPDC 1表达呈正相关。通过小干扰RNA敲低CCL 20或CCR 6可逆转HCC细胞中DEPDC 1过表达的作用。此外，它表明，条件培养基DEPDC 1上调Li-7和Hep 3B细胞导致血管生成在体外，而CCL 20敲低Li-7和Hep 3B细胞或CCR 6敲低人脐静脉内皮细胞逆转DEPDC 1过表达的血管生成作用。总之，DEPDC 1通过CCL 20/CCR 6通路促进HCC中的细胞增殖、侵袭和血管生成。
DEP domain containing 1 (DEPDC1) functions as an oncogene in hepatocellular carcinoma (HCC). However, the underlying mechanism of DEPDC1 remains largely unknown. The present study revealed that DEPDC1 knockdown inhibited HCC cell proliferation, colony formation and invasion in vitro and suppressed the growth of HCC xenografts in vivo. Furthermore, DEPDC1 overexpression promoted HCC cell proliferation, colony formation and invasion. DNA microarray, reverse transcription-quantitative-PCR and western blotting results demonstrated that DEPDC1 knockdown in Huh-7 significantly inhibited the expression of chemokine (C-C motif) ligand 20 (CCL20) and chemokine (C-C motif) receptor 6 (CCR6). In addition, the expression of CCL20 and CCR6 were upregulated in HCC tissues and cell lines, and were positively correlated with DEPDC1 expression. CCL20 or CCR6 knockdown via small interfering RNA reversed the effects of DEPDC1 overexpression in HCC cells. Furthermore, it was revealed that conditioned medium from DEPDC1 upregulated Li-7 and Hep3B cells led to angiogenesis in vitro, whereas CCL20 knockdown in Li-7 and Hep3B cells or CCR6 knockdown in human umbilical vein endothelial cells reversed the angiogenic effect of DEPDC1 overexpression. In conclusion, DEPDC1 facilitated cell proliferation, invasion and angiogenesis via the CCL20/CCR6 pathway in HCC.