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

 Dasom Son  ;  Yesol Kim  ;  Sera Lim  ;  Hyeok-Gu Kang  ;  Da-Hyun Kim  ;  Jee Won Park  ;  Woosung Cheong  ;  Hyun Kyung Kong  ;  Wonshik Han  ;  Woong-Yang Park  ;  Kyung-Hee Chun  ;  Jong Hoon Park 
 Cancer Letters, Vol.454 : 224-233, 2019 
Journal Title
 Cancer Letters 
Issue Date
AMPKα ; Arrestin beta 1 ; Triple negative breast cancer ; miR-374a-5p
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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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyeok Gu(강혁구) ORCID logo https://orcid.org/0000-0002-3187-6844
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
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