MicroRNA-138 suppresses glioblastoma proliferation through downregulation of CD44.
Sci Rep
; 11(1): 9219, 2021 04 28.
Article
em En
| MEDLINE
| ID: mdl-33911148
ABSTRACT
Tumor suppressive microRNAs (miRNAs) are increasingly implicated in the development of anti-tumor therapy by reprogramming gene network that are aberrantly regulated in cancer cells. This study aimed to determine the therapeutic potential of putative tumor suppressive miRNA, miR-138, against glioblastoma (GBM). Whole transcriptome and miRNA expression profiling analyses on human GBM patient tissues identified miR-138 as one of the significantly downregulated miRNAs with an inverse correlation with CD44 expression. Transient overexpression of miR-138 in GBM cells inhibited cell proliferation, cell cycle, migration, and wound healing capability. We unveiled that miR-138 negatively regulates the expression of CD44 by directly binding to the 3' UTR of CD44. CD44 inhibition by miR-138 resulted in an inhibition of glioblastoma cell proliferation in vitro through cell cycle arrest as evidenced by a significant induction of p27 and its translocation into nucleus. Ectopic expression of miR-138 also increased survival rates in mice that had an intracranial xenograft tumor derived from human patient-derived primary GBM cells. In conclusion, we demonstrated a therapeutic potential of tumor suppressive miR-138 through direct downregulation of CD44 for the treatment of primary GBM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Glioblastoma
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Receptores de Hialuronatos
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MicroRNAs
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article