Reduced miR-550a-3p leads to breast cancer initiation, growth, and metastasis by increasing levels of ERK1 and 2.
Oncotarget
; 7(33): 53853-53868, 2016 Aug 16.
Article
in En
| MEDLINE
| ID: mdl-27462780
ABSTRACT
Hyperactivation of the Ras/ERK pathway contributes to breast cancer initiation and progression, and recent evidence suggests aberrant signaling of miRNAs that regulate the Ras/ERK pathway play important roles during carcinogenesis and cancer progression. In this study, we demonstrate that miR-550a-3p expression is negatively correlated with levels of ERK1 and ERK2, two pivotal effectors in the Ras/ERK pathway. MiR-550a-3p gradually decreased during breast cancer initiation and progression and this reduction was a prognostic indicator of poorer overall survival (OS) and disease-free survival (DFS) among breast cancer patients. Our mechanistic studies demonstrated that miR-550a-3p exerts its tumor-suppressor role by directly repressing ERK1 and ERK2 protein expression, thereby suppressing the oncogenic ERK/RSK cascades, which reduced breast cancer cell viability, survival, migration, invasion, tumorigenesis, and metastasis. The inhibitory effects of miR-550a-3p were rescued by ectopic expression of ERK1 and/or ERK2. The novel connection between miR-550a-3p and ERK defines a new diagnostic and prognostic role for miR-550a-3p and highlights ERK inhibition as a candidate therapeutic target for breast cancers exhibiting hyperactivated Ras/ERK signaling.
Key words
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Mitogen-Activated Protein Kinase 1
/
MicroRNAs
/
Mitogen-Activated Protein Kinase 3
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Oncotarget
Year:
2016
Document type:
Article