ArticleOncoTargets and therapy2020
Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Lipopolysaccharide-binding protein (LBP): a prognostic biomarker for gastric cancer linked to immune infiltration.BMC gastroenterology · 2025Article
- Targeting USP8 Inhibits O-GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- USP8 inhibitor-induced DNA damage activates cell cycle arrest, apoptosis, and autophagy in esophageal squamous cell carcinoma.Cell biology and toxicology · 2023Article
- USP8 positively regulates hepatocellular carcinoma tumorigenesis and confers ferroptosis resistance through β-catenin stabilization.Cell death & disease · 2023Article
- Targeting ubiquitin-specific protease 8 sensitizes anti-programmed death-ligand 1 immunotherapy of pancreatic cancer.Cell death and differentiation · 2023Article
- Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth.Open life sciences · 2023Article
- Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha.Journal of oncology · 2023Article
- Usp8 promotes tumor cell migration through activating the JNK pathway.Cell death & disease · 2022Article
- Destruction or Reconstruction: A Subtle Liaison between the Proteolytic and Signaling Role of Protein Ubiquitination in Spermatogenesis.Advances in experimental medicine and biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUbiquitin specific peptidase 8 (USP8) has been reported to induce the degradation of several receptor tyrosine kinases such as epidermal growth factor receptor (EGFR), among which human epidermal growth factor receptor-3 (HER-3) is one of them. However, the role and functional mechanisms of USP8 and HER-3 in gastric cancer (GC) remain unknown.
objectiveTo explore the function and mechanism of USP8 and HER-3 in the progression of GC. MATERIALS AND
methodsEighty-eight patients with histologically confirmed GC were recruited for this study. Tumor samples and GC cell lines were used to detect USP8 and HER-3 levels. MGC803 (HER-3 negative GC cell) was selected as the control group and NCI-N87, MKN-45 and AGS (HER-3 positive GC cells) as the experimental group. USP8i and si-RNA were then used to down-regulate USP8 in each group. Apoptosis and cell-cycle experiments were performed to detect the effects of USP8 on GC cells. Cytotoxicity Assay Kit (MTT) and colony formation assays were used to analyze cell proliferation. Cell migration and invasion ability were examined by wound healing. The expression of related mRNA and protein was detected by Western blot and quantitative real-time PCR (qRT-PCR). In vivo experiments were used to examine the effect of USP8 and HER-3.
resultsPatients with high expression of USP8 or HER-3 tumors alone died earlier than those with low expression and the patients with both USP8 and HER-3 high expression had a shorter overall survival than those with the opposite pattern (both USP8 and HER-3 low expression). Down-regulation of USP8 inhibited cell proliferation and cell metastasis and also reduced the HER-3 expression. We also observed that down-regulation of USP8 inhibited the proliferation of GC cells which highly expressed HER-3. Moreover, down-regulation of USP8 could promote the apoptosis of HER3-positive GC cells and inhibit the proliferation of them by affecting the cell-cycle. In vivo studies demonstrated that down-regulation of USP8 inhibited HER-3 positive tumors growth.
conclusionDown-regulation of USP8 inhibits HER-3 positive GC cells proliferation in vivo and in vitro, which indicate that USP8 represents a feasible choice as a therapeutic target for HER-3 positive GC cells.
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