WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma

Zhang, Li; Wu, Zongyin; Ma, Zhao; Liu, Hongtao; Wu, Yahong; Zhang, Qinxian

doi:10.1007/s13277-014-2696-0

Cited by 32 publications

(28 citation statements)

References 47 publications

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“…Notably, high WWP1 expression predicted a higher metastatic potential and poor prognosis in patients with CSCC, which differed from the results of a previous study in breast cancer patients, 16 but was consistent with a study in patients with gastric carcinoma. 13 These findings imply that WWP1 may represent a new biomarker for metastasis and prognosis in patients with CSCC.…”

Section: Discussionmentioning

confidence: 90%

WW domain-containing E3 ubiquitin protein ligase 1 depletion evokes antitumor effect in cutaneous squamous cell carcinoma by inhibiting signal transducer and activator of transcription 3 signaling pathway

et al. 2018

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ObjectivesWW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been implicated in tumor progression. We aimed to investigate the role of WWP1 in cutaneous squamous cell carcinoma (CSCC).MethodsWWP1 gene and protein levels were detected using semi-quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blotting. The effects of WWP1 on cell cycle, apoptosis, cell migration and invasion were examined by flow cytometry, wound healing and Transwell assays, respectively. The antitumor efficacy of WWP1 small interfering RNA was determined in CSCC tumor xenografts in mice.ResultsWWP1 expression was significantly higher in CSCC tissues and cells than in normal skin and cells, respectively. WWP1 expression was significantly associated with histological grade, invasion depth and lymph node metastasis in patients with CSCC. High expression predicted metastatic potential and an unfavorable prognosis. WWP1 downregulation suppressed tumor growth in vitro and in vivo, reduced cell migration and invasion, arrested the cell cycle in G0/G1 and induced apoptosis in A431 cells. WWP1 depletion also decreased phosphorylated signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-2, cyclin D1 and Bcl-2, but did not affect total STAT3.ConclusionsWWP1 is a potential target for the diagnosis, prognosis and therapy of patients with CSCC.

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Section: Discussionmentioning

confidence: 90%

WW domain-containing E3 ubiquitin protein ligase 1 depletion evokes antitumor effect in cutaneous squamous cell carcinoma by inhibiting signal transducer and activator of transcription 3 signaling pathway

et al. 2018

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“…In addition, WWP1 is also frequently amplified in oral cancer [113]. Furthermore, increased WWP1 mRNA and protein levels have been reported in hepatocarcinoma cell lines and tissues [114], as well as in gastric tumors [115]. Collectively, these findings strongly suggest a role for WWP1 in oncogenesis.…”

Section: Wwpsmentioning

confidence: 86%

Molecular functions of NEDD4 E3 ubiquitin ligases in cancer

Zou

Levy-Cohen

Blank

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

106

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“…WWP1 delays cellular senescence and negatively regulates the TGFβ signaling pathway, which regulates cell proliferation, differentiation, apoptosis, and migration in numerous cell types [16, 17]. Furthermore, it has been reported that WWP1 acts as an oncogenic factor in GC [18]. In the present study, we used bioinformatic prediction and experimental confirmation studies to demonstrate that WWP1 plays a pivotal role in human GC and is a putative direct target of miR-584-5p.…”

Section: Introductionmentioning

confidence: 85%

Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer

Zheng

Wei

et al. 2017

J Exp Clin Cancer Res

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BackgroundMicroRNAs are endogenously expressed, small non-coding RNAs that modulate gene expression by targeting specific mRNAs, resulting in translational repression or mRNA degradation. Although miR-584-5p has been reported to play a vital role in various malignancies, its role and the molecular mechanisms underlying the effects of miR-584-5p in gastric cancer (GC) remain to be clarified. In this study, we investigated the role of miR-584-5p in GC.MethodsThe expression of miR-584-5p and its specific target gene were determined in human GC specimens and cell lines by microRNA real-time polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR) and Western blot. The effects of miR-584-5p depletion or ectopic expression on GC proliferation were evaluated in vitro using CCK-8 proliferation assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assays and cell-cycle assays and the in vivo effects were investigated using a mouse tumorigenicity model. Cell apoptosis was evaluated by in vitro flow cytometric analysis, cell viability assays and in vivo TUNEL assays. Luciferase reporter assays were employed to identify interactions between miR-584-5p and its specific target gene.ResultsA series of in vitro and in vivo gain- and loss-of-function assays revealed that miR-584-5p inhibited GC cell proliferation, while apoptosis was induced. Luciferase reporter assays and Western blot analysis revealed WWP1 to be a direct target of miR-584-5p. The effects of miR-584-5p-mimic were rescued by WWP1 overexpression. In contrast, the effects of the miR-584-5p-inhibitor were impaired by WWP1-shRNA. Furthermore, miR-584-5p expression levels correlated negatively with WWP1 protein expression in GC tissues and GC cell lines. A series of investigations indicated that miR-584-5p promoted senescence and activated the TGFβ signaling pathway by downregulation of WWP1.ConclusionTaken together, these results suggest that downregulation of miR-584-5p contributes to tumor progression by downregulation of WWP1, thus, highlighting the potential of miR-584-5p as a therapeutic target for human GC.

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WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma

Cited by 32 publications

References 47 publications

WW domain-containing E3 ubiquitin protein ligase 1 depletion evokes antitumor effect in cutaneous squamous cell carcinoma by inhibiting signal transducer and activator of transcription 3 signaling pathway

WW domain-containing E3 ubiquitin protein ligase 1 depletion evokes antitumor effect in cutaneous squamous cell carcinoma by inhibiting signal transducer and activator of transcription 3 signaling pathway

Molecular functions of NEDD4 E3 ubiquitin ligases in cancer

Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer

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