Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 505, Issue 1, Pages 302-308Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.09.103
Keywords
Breast cancer; miR-1247-5p; DVL1; Wnt/beta-catenin signaling
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Funding
- National Natural Science Foundation of China [81472475]
- Chongqing Science and Technology Commission [cstc2016jcyjA0313]
- Scientific Research Foundation of Chongqing Medical University [201408]
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The abnormal expression of microRNAs is a key hallmark of breast cancer. Nevertheless, the biological roles of miR-1247-5p in breast cancer remain unknown. In this study, we revealed that miR-1247-5p expression was markedly decreased in breast cancer. It was a valuable diagnostic biomarker for breast cancer with the area under the curve of more than 0.80. Reduced miR-1247-5p expression was significantly correlated with patient age, tumor size, and poor prognosis in The Cancer Genome Atlas cohort including 839 breast cancer patients. Multivariate Cox regression analysis demonstrated that miR-1247-5p was an independent prognostic indicator for overall survival (hazard radio [HR] = 1.683, 95% confidence interval [CI] = 1.087-2.606, p = 0.020) and recurrence-free survival (HR = 2.496, 95% Cl = 1.576 -3.951, p < 0.001). Moreover, functional studies showed that overexpression of miR-1247-5p inhibited proliferation and induced apoptosis in breast cancer cells. Bioinformatics analysis and mechanistic investigations revealed that Dishevelled 1 (DVL1) was a direct target of miR-1247-5p. Inhibition of DVL1 by miR-1247-5p resulted in the suppression of Wnt/beta-catenin signaling, whereas overexpression of DVL1 abrogated the miR-1247-5p-mediated effect. These data reveal that miR-1247-5p, as an oncosuppressor in breast cancer, may be a promising prognostic biomarker and therapeutic target. (C) 2018 Elsevier Inc. All rights reserved.
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