Journal
CANCER LETTERS
Volume 454, Issue -, Pages 224-233Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.04.006
Keywords
miR-374a-5p; Triple negative breast cancer; Arrestin beta 1; AMPK alpha
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Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIP) [2016R1A2A1A05005295, 2016R1A5A1011974]
- National Research Foundation of Korea [2016R1A2A1A05005295] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Triple negative breast cancer (TNBC) has higher aggressiveness and poorer outcomes compared with other subtypes of breast cancer. However, the genomic and molecular aberrations of TNBC are largely unknown. In this study, miR-374a-5p was discovered as a novel TNBC-specific miRNA and its functions and the molecular mechanisms involved were investigated. Combined gene expression profiling of miRNA-microarray and human transcriptome dataset analysis revealed that miR-374a-5p is specifically upregulated in TNBC patients. Functional studies using in vitro and in vivo models indicated that upregulated miR-374a-5p promotes tumor progression in TNBC. miR-374a-5p was also found to directly target arrestin beta 1 (ARRB1) that is specifically downregulated in TNBC patients in several human genomic datasets. Overexpressed ARRB1 reduced TNBC cell growth and migration, and the ARRB1 expression level is inversely correlated with the histological grade of the breast cancer and positively associated with TNBC patient survival, suggestive of a tumor-suppressive function of ARRB1 in breast cancer. Interestingly, increased ARRB1 activates AMPK in TNBC cells, associated with the expression of miR-374a-5p. Taken together, the findings suggest that miR-374a-5p is a potential prognostic marker of TNBC.
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