MicroRNA-1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non-small-cell lung cancer.
Cell Prolif
; 51(6): e12502, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30069987
OBJECTIVES: Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR-1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR-1258 in non-small-cell lung cancer remains unclear. METHODS: The differential expression of miR-1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT-PCR and ISH. Flow cytometry and CCK-8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR-1258. Potential targets of miR-1258 were verified by dual luciferase reporter assay, qRT-PCR, IHC and Western blotting. RESULTS: In vitro and in vivo gain- and loss-of-function assays suggested that miR-1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR-1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR-1258. In contrast, miR-1258 inhibitor significantly reversed si-GRB2-induced GRB2 down-regulation. Mechanistically, overexpression of miR-1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway. CONCLUSIONS: Our results indicate that miR-1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Carcinoma Pulmonar de Células não Pequenas
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MicroRNAs
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Proteína Adaptadora GRB2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Prolif
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido