DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway

Guo,Wubin; Li,Hui; Liu,Huan; Ma,Xin; Yang,Sijin; Wang,Ziwei

doi:10.3892/or.2019.7221

DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway

Authors:
- Wubin Guo
- Hui Li
- Huan Liu
- Xin Ma
- Sijin Yang
- Ziwei Wang
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Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Research Laboratory of Biomedical Engineering, The TCM Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of General Surgery, The TCM Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Cardiovascular Medicine, The TCM Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: July 5, 2019 https://doi.org/10.3892/or.2019.7221
Pages: 1075-1089
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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