Oncotarget

Research Papers:

Reduced miR-550a-3p leads to breast cancer initiation, growth, and metastasis by increasing levels of ERK1 and 2

Jar-Yi Ho, Ren-Jun Hsu, Chih-Hsi Wu, Guo-Shiou Liao, Hong-Wei Gao, Tong-Hong Wang and Cheng-Ping Yu _

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Oncotarget. 2016; 7:53853-53868. https://doi.org/10.18632/oncotarget.10793

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Abstract

Jar-Yi Ho1,*, Ren-Jun Hsu1,2,*, Chih-Hsi Wu1, Guo-Shiou Liao3, Hong-Wei Gao1, Tong-Hong Wang4, Cheng-Ping Yu1,2

1Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

2Biobank Management Center of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

3Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan

4Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Cheng-Ping Yu, email: cpyupath@yahoo.com.tw

Keywords: miR-550a-3p, ERK1, ERK2, Ras/ERK signaling, breast cancer

Received: March 29, 2016    Accepted: July 10, 2016    Published: July 23, 2016

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.


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