Reduced microRNA 375 in colorectal cancer upregulates metadherin-mediated signaling.
World J Gastroenterol
; 25(44): 6495-6507, 2019 Nov 28.
Article
em En
| MEDLINE
| ID: mdl-31802830
ABSTRACT
BACKGROUND:
The human microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) and we have previously shown that MIR375 is a CRC-associated miRNA. The metadherin (MTDH) is a candidate target gene of MIR375.AIM:
To investigate the interaction and function between MIR375 and MTDH in human CRC.METHODS:
A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression. The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR), western blotting, or immunohistochemistry.RESULTS:
MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls. We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways [BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha (PIK3CA)-AKT] in CRC cells. Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha, which further upregulated NFKB1 and RELA expression in CRC cells.CONCLUSION:
Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression. Thus, MIR375 may be of therapeutic value in treating human CRC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Retais
/
Regulação Neoplásica da Expressão Gênica
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Proteínas de Ligação a RNA
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Neoplasias do Colo
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MicroRNAs
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Proteínas de Membrana
Limite:
Aged
/
Female
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Humans
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Male
Idioma:
En
Revista:
World J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Coréia do Sul