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

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.

ABRO1 stabilizes the deubiquitinase BRCC3 through inhibiting its degradation mediated by the E3 ubiquitin ligase WWP2

“…Accumulating evidence has indicated that WWP2 plays a crucial role in the pathogenesis in various types of tumors; however, the underlying mechanisms are not fully understood [43]. On the one hand, the oncogenic role of WWP2 has been well documented in many types of tumors, including oral cancer, endometrial cancer, liver cancer, lung cancer, and glioma [44][45][46][47][48]. On the other hand, WWP2 has been shown to act as a tumor-suppressive gene in ovarian cancer and multiple myeloma [49,50].…”

Insulin receptor isoform A favors tumor progression in human hepatocellular carcinoma by increasing stem/progenitor cell features

“…Among the most stimulated inflammation-related genes, CXCL10 codes for a chemokine involved in the recruitment of immune cells and associated with HCC recurrence and poor survival [36]. CXCL10 and its receptor CXCR3 were reported to promote migration and invasion in HCC cell lines [37,38].…”

Systematic analyses of a novel lncRNA‐associated signature as the prognostic biomarker for Hepatocellular Carcinoma

“…The large‐scale genome analyses have revealed the molecular characteristics associated with HCC OS . However, most studies focused on miRNA, mRNA, gene, and protein expression . With knowledge growing, the functional role of lncRNAs in tumorigenesis and development also represents a significant untapped resource for HCC prognosis.…”

“…[23][24][25] However, most studies focused on miRNA, mRNA, gene, and protein expression. [26][27][28][29][30] T A B L E 3 (Continued) growing, the functional role of lncRNAs in tumorigenesis and development also represents a significant untapped resource for HCC prognosis.…”