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Cancer Lett. 2019 Jul 10;454:224-233. doi: 10.1016/j.canlet.2019.04.006. Epub 2019 Apr 17.

miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer.

Author information

1
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
2
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
3
Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
4
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
5
Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunwan University, Seoul, Republic of Korea; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
6
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: parkjh@sookmyung.ac.kr.

Abstract

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.

KEYWORDS:

AMPKα; Arrestin beta 1; Triple negative breast cancer; miR-374a-5p

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