title: 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.
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China. xushengqian162@163.com.
authors.forename: Sheng-Qian
authors.initials: SQ
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: De-Biao
authors.initials: DB
authors.lastname: Pan
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Guan-Xiong
authors.initials: GX
authors.lastname: Ye
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Chao-Jun
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Lishui, 15 Public Street, Liandu District, Lishui, 323000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051379:Mice; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C465283:WWP2 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Carcinogenesis; Chemokine signaling pathway; Liver cancer; WWP2