Tumor suppressor miR-139-5p targets Tspan3 and regulates the progression of acute myeloid leukemia through the PI3K/Akt pathway.
J Cell Biochem
; 120(3): 4423-4432, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30367526
ABSTRACT
Dysregulation of microRNAs is closely implicated in the initiation and progression of human cancers including acute myeloid leukemia (AML). Though miR-139-5p was reported to be a potent tumor suppressor in adult AML, its underlying molecular mechanism in AML remains to be further defined. Herein, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were conducted to determine the expressions of miR-139-5p and tetraspanin3 (Tspan3) in AML patients and cells. Luciferase reporter assay, qRT-PCR, and Western blot analysis were carried out to detect the interaction between miR-139-5p and Tspan3. Cell proliferation, cell cycle distribution, invasion, and migration were evaluated by cell counting kit-8, flow cytometry, transwell invasion, and migration assays, respectively. Western blot analysis was conducted to determine phosphorylated-protein kinase B (Akt) and Akt levels. We found that a significant reduction in miR-139-5p expression and a prominent increase in Tspan3 expression were observed in AML patients and cells. Tspan3 was confirmed as a direct target of miR-139-5p and was negatively modulated by miR-139-5p. Rescue experiments showed that overexpression of miR-139-5p constrained cell proliferation, invasion and migration capabilities, and induced cell cycle arrest at the S phase in AML cells, which were partially reversed by Tspan3 overexpression. In addition, we found that miR-139-5p suppressed the phosphoinositide 3-kinase (PI3K)/Akt pathway in AML cells by targeting Tspan3. In conclusion, our study concluded that miR-139-5p suppressed the leukemogenesis in AML cells by targeting Tspan3 through inactivation of the PI3K/Akt pathway, providing a better understanding of AML progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Neoplásico
/
Leucemia Mieloide Aguda
/
Transducción de Señal
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Genes Supresores de Tumor
/
MicroARNs
/
Tetraspaninas
Límite:
Humans
Idioma:
En
Revista:
J Cell Biochem
Año:
2019
Tipo del documento:
Article
País de afiliación:
China