Intronic miRNA-641 controls its host Gene's pathway PI3K/AKT and this relationship is dysfunctional in glioblastoma multiforme.
Biochem Biophys Res Commun
; 489(4): 477-483, 2017 08 05.
Article
en En
| MEDLINE
| ID: mdl-28576488
ABSTRACT
MicroRNAs have established their role as important regulators of the epigenome. A considerable number of human miRNA genes are found in intronic regions of protein-coding host genes, in many cases adopting their regulatory circuitry. However, emerging evidence foreshadows an unprecedented importance for this relationship Intronic miRNAs may protect the cell from overactivation of the respective host pathway, a setting that may trigger tumor development. AKT2 is a well-known proto-oncogene central to the PI3K/AKT pathway. This pathway is known to promote tumor growth and survival, especially in glioblastoma. Its intronic miRNA, hsa-miR-641, is scarcely investigated, however. We hypothesized that miR-641 regulates its host AKT2 and that this regulation may become dysfunctional in glioblastoma. We found that indeed miR-641 expression differs significantly between GBM tissue and normal brain samples, and that transfection of glioma cells with miR-641 antagonizes the PI3K/AKT pathway. Combining clinical samples, cell cultures, and biomolecular methods, we could show that miR-641 doesn't affect AKT2's expression levels, but down-regulates kinases that are necessary for AKT2-activation, thereby affecting its functional state. We also identified NFAT5 as a miR-641 regulated central factor to trigger the expression of these kinases and subsequently activate AKT2. In summary, our study is the first that draws a connecting line between the proto-oncogene AKT2 and its intronic miRNA miR-641 with implication for glioblastoma development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glioblastoma
/
Fosfatidilinositol 3-Quinasas
/
MicroARNs
/
Proteínas Proto-Oncogénicas c-akt
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2017
Tipo del documento:
Article