A minicircuitry comprised of microRNA-9 and SIRT1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.
Eur Rev Med Pharmacol Sci
; 21(4): 786-794, 2017 02.
Article
en En
| MEDLINE
| ID: mdl-28272704
ABSTRACT
OBJECTIVE:
The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML. PATIENTS ANDMETHODS:
Expression of miR-9 and SIRT1 in AE-positive AML patients, healthy donors and AML cell lines were detected by qPCR. Relevance between miR-9 and SIRT1 was assessed by plasmid transfection, Western blot and correlation analysis. Luciferase assay was used to confirm the target gene of miR-9. Knockdown of SIRT1 in different cell lines was achieved by shRNA transfection and CCK-8 assay was used to investigate the effects on cell proliferation.RESULTS:
The miR-9 expression was lower in AE-positive cell lines compared to that in other AE-negative AML cell lines, while expression of SIRT1 was higher in AE-positive cell lines. Expression of miR-9 was also downregulated in adult primary t(8;21) AML patients compared to healthy donors. The over-expression of miR-9 decreased luciferase activity of wild-type SIRT1, which was recovered after transfection with mutant SIRT1. The miR-9 directly targets SIRT1 by binding to its 3'-untranslated region and reducing its protein levels. Importantly, miR-9 and SIRT1 mRNA levels were inversely correlated in AE-positive AML cell lines and t(8;21) AML primary leukemia cells. Knockdown of SIRT1 levels using shSIRT1 inhibited cell proliferation in AE-positive AML cell lines.CONCLUSIONS:
SIRT1 is the target gene of miR-9 and the signaling pathway connecting miR-9 and SIRT1 is a therapeutic target for t(8;21) AML.
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Bases de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
MicroARNs
/
Sirtuina 1
Límite:
Humans
Idioma:
En
Revista:
Eur Rev Med Pharmacol Sci
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China