Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth.
Int J Colorectal Dis
; 27(1): 21-30, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21773699
ABSTRACT
PURPOSE:
Increasing experimental evidences suggest that ubiquitin-specific protease 22 (USP22), a cancer stem cell marker, plays a crucial role in pathological processes of epithelial malignancies and other solid tumors, which makes it a potential target for cancer therapy. The aim of this study was to study the roles of USP22 in human colorectal cancer cell line HCT116 by suppressing USP22 expression with micro-interfering RNA (miRNA).METHODS:
With the knock-down of USP22, the changes of cellular proliferation, cell cycle, cell apoptosis, and major vault protein (MVP) expression were investigated. Furthermore, a tumor xenograft model in nude mice was injected with USP22 miRNA silencing vector and the immunohistochemical staining was performed to evaluate the USP22 expression in the tumor.RESULTS:
The knock-down of USP22 protein expression by miRNA resulted in the inhibition of cellular proliferation, the accumulation of cells in the G1 phase, the reduction of apoptosis, and the down-regulation of MVP expression. Furthermore, with orthotopic mice as a model, tumor growth was suppressed when USP22 miRNA silencing vector was injected. Immunohistochemical analyses of tumor sections revealed that USP22 expression in animals decreased when USP22 expression was inhibited by miRNA.CONCLUSION:
These results support the hypothesis that USP22 plays a crucial role in tumor formation and growth by regulating cell proliferation with USP22-dependent signaling pathway. Furthermore, USP22 acts as a major transcriptional factor to regulate MVP drug resistant gene. Taken together, targeting USP22 may offer additional possibilities in cancer therapy.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Tioléster Hidrolasas
/
Neoplasias Colorrectales
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MicroARNs
/
Técnicas de Silenciamiento del Gen
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Int J Colorectal Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2012
Tipo del documento:
Article