CD9 knockdown suppresses cell proliferation, adhesion, migration and invasion, while promoting apoptosis and the efficacy of chemotherapeutic drugs and imatinib in Ph+ ALL SUPB15 cells.
Mol Med Rep
; 22(4): 2791-2800, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32945456
ABSTRACT
Philadelphia chromosomepositive acute lymphoblastic leukemia (Ph+ ALL) is regarded as a prognostically unfavorable subgroup, as this ALL subgroup has an increased risk of relapse/refractory disease. CD9, which belongs to the tetraspanin membrane proteins, is implicated in several pathological processes, including tumor progression. However, the role of CD9 in the pathogenesis of Ph+ ALL and the potential benefit of applying CD9targeted RNA interference strategies for treatment of Ph+ ALL require further investigation. The aim of the present study was to determine the effects of CD9 on leukemic cell progression and the efficacy of therapeutic agents in Ph+ ALL cells, in addition to assessing the in vitro antileukemia activity of CD9targeted RNA interference in Ph+ ALL cells. In the present study, a lentiviral short hairpin RNA (shRNA) expression vector targeting CD9 gene in Ph+ ALL SUPB15 cells was constructed. The present results demonstrated that treatment of SUPB15 cells with lentiviralmediated shRNA against CD9 decreased CD9 mRNA and protein expression compared with the shControl cells transduced with a blank vector. In addition, CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the efficacy of chemotherapeutic drugs (such as vincristine, daunorubicin, cyclophosphamide and dexamethasone) and the tyrosine kinase inhibitor imatinib in SUPB15 cells. Furthermore, CD9 knockdown suppressed cell proliferation and promoted apoptosis in SUPB15 cells via a p53dependent pathway. These findings suggested that gene silencing of CD9 using a shRNAexpressing lentivirus vector may provide a promising treatment for Ph+ ALL.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Interferente Pequeno
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Tetraspanina 29
/
Mesilato de Imatinib
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article