Tumor Biology

, Volume 37, Issue 5, pp 6787–6799 | Cite as

Silencing of WWP2 inhibits adhesion, invasion, and migration in liver cancer cells

  • Yong Qin
  • Sheng-qian Xu
  • De-biao Pan
  • Guan-xiong Ye
  • Cheng-jun Wu
  • Shi Wang
  • Chao-jun Wang
  • Jin-yan Jiang
  • Jing Fu
Original Article

Abstract

The role and clinical implication of the WWP2 E3 ubiquitin ligase in liver cancer are poorly understood. In the current study, we investigated the expression level of WWP2 and its functions in cell adhesion, invasion, and migration in liver cancer. We used real-time PCR to detect the expression of WWP2 in liver cancer and adjacent samples from the People’s Hospital of Lishui and also analyzed The Cancer Genome Atlas (TCGA) RNA-seq data by bioinformatics. Migration and invasion were detected by transwell analysis. We detected a strong WWP2 expression in tumor tissues of the People’s Hospital of Lishui, and the survival rate was significantly higher in patients with lower WWP2-expressing tumors. WWP2 small hairpin RNA (shRNA) lentivirus stably infected cells (shWWP2), Huh7, showed slower growth speed compared with scramble control-infected cells in a xenograft mouse model. Knockdown of WWP2 Huh7 and BEL-7404 cells demonstrated a reduction in adhesion, invasion, and migration. Gene set enrichment analysis (GSEA) showed that WWP2 is positively correlated to cancer-related pathways including the chemokine signaling pathway. WWP2 also regulated MMP-9, caspase-9, CXCR3, and CCR5 expression in liver cancer cells. In addition, knockdown of CXCR3 and CCR5 significantly inhibited cell proliferation, adhesion, invasion, and migration in Huh7 and BEL-7404 cells. Our data suggest that targeting of WWP2 may be a therapeutic strategy for liver cancer treatment.

Keywords

Liver cancer WWP2 Carcinogenesis Chemokine signaling pathway 

Notes

Acknowledgments

This study was supported by the Project of science and technology of Zhejiang Province public welfare (2014c3316).

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

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13277_2015_4547_MOESM2_ESM.xls (74 kb)
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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yong Qin
    • 1
  • Sheng-qian Xu
    • 1
  • De-biao Pan
    • 1
  • Guan-xiong Ye
    • 1
  • Cheng-jun Wu
    • 1
  • Shi Wang
    • 1
  • Chao-jun Wang
    • 1
  • Jin-yan Jiang
    • 1
  • Jing Fu
    • 1
  1. 1.Department of Hepatobiliary SurgeryPeople’s Hospital of LishuiLishuiChina

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