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

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...

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Bibliographic Details
Published in:	Cancer letters Vol. 454; pp. 224 - 233
Main Authors:	Son, Dasom, Kim, Yesol, Lim, Sera, Kang, Hyeok-Gu, Kim, Da-Hyun, Park, Jee Won, Cheong, Woosung, Kong, Hyun Kyung, Han, Wonshik, Park, Woong-Yang, Chun, Kyung-Hee, Park, Jong Hoon
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier B.V 10-07-2019 Elsevier Limited
Subjects:	AMP-Activated Protein Kinases - genetics AMP-Activated Protein Kinases - metabolism AMPKα Arrestin Arrestin beta 1 beta-Arrestin 1 - biosynthesis beta-Arrestin 1 - genetics beta-Arrestin 1 - metabolism Breast cancer Cell growth Cell Line, Tumor Cell migration Cell Movement - physiology Cell Proliferation - physiology Cell Survival - physiology Disease Progression DNA microarrays Enzyme Activation Female Gene expression Genes HEK293 Cells Humans Kinases MCF-7 Cells Medical prognosis Metastasis MicroRNAs - genetics MicroRNAs - metabolism Migration miR-374a-5p miRNA Molecular modelling Proteins Studies Triple negative breast cancer Triple Negative Breast Neoplasms - genetics Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology Up-Regulation United States > US South Korea Arrestin beta 1 Lum A miR-374a-5p AMPKα Lum B 3′UTR miRNA ARRB1 TNBC HER2 Triple negative breast cancer
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Summary:	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. •miR-374a-5p as a novel TNBC-specific upregulated miRNA.•miR-374a-5p promotes tumor progression and directly target arrestin beta 1 in TNBC.•miR-374a-5p/ARRB1 axis regulates AMPK activation in TNBC.•miR-374a-5p could be a novel molecular marker and therapeutic target for TNBC.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2019.04.006