Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4.
Infect Agent Cancer
; 16(1): 63, 2021 Nov 07.
Article
en En
| MEDLINE
| ID: mdl-34743754
BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC. METHODS: In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples. RESULTS: Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4. CONCLUSION: Silencing of UBE2D1 inhibited cell migration through transforming growth factor ß (TGF-ß)/SMAD4 signaling pathway in GC.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
/
Screening_studies
Idioma:
En
Revista:
Infect Agent Cancer
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido