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

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)224-233
Number of pages10
JournalCancer Letters
Volume454
DOIs
StatePublished - 10 Jul 2019

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Triple Negative Breast Neoplasms
Neoplasms
Gene Expression Profiling
Breast Neoplasms
MicroRNAs
beta-Arrestin 1
AMP-Activated Protein Kinases
Cell Movement
Down-Regulation

Keywords

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

Cite this

Son, D., Kim, Y., Lim, S., Kang, H. G., Kim, D. H., Park, J. W., ... Park, J. H. (2019). miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer. Cancer Letters, 454, 224-233. https://doi.org/10.1016/j.canlet.2019.04.006
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. / miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer. In: Cancer Letters. 2019 ; Vol. 454. pp. 224-233.
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title = "miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer",
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",
author = "Dasom Son and Yesol Kim and Sera Lim and Kang, {Hyeok Gu} and Kim, {Da Hyun} and Park, {Jee Won} and Woosung Cheong and Kong, {Hyun Kyung} and Wonshik Han and Park, {Woong Yang} and Chun, {Kyung Hee} and Park, {Jong Hoon}",
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year = "2019",
month = "7",
day = "10",
doi = "10.1016/j.canlet.2019.04.006",
language = "English",
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Son, D, Kim, Y, Lim, S, Kang, HG, Kim, DH, Park, JW, Cheong, W, Kong, HK, Han, W, Park, WY, Chun, KH & Park, JH 2019, 'miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer', Cancer Letters, vol. 454, pp. 224-233. https://doi.org/10.1016/j.canlet.2019.04.006

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

In: Cancer Letters, Vol. 454, 10.07.2019, p. 224-233.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - miR-374a-5p promotes tumor progression by targeting ARRB1 in triple negative breast cancer

AU - Son, Dasom

AU - Kim, Yesol

AU - Lim, Sera

AU - Kang, Hyeok Gu

AU - Kim, Da Hyun

AU - Park, Jee Won

AU - Cheong, Woosung

AU - Kong, Hyun Kyung

AU - Han, Wonshik

AU - Park, Woong Yang

AU - Chun, Kyung Hee

AU - Park, Jong Hoon

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2019/7/10

Y1 - 2019/7/10

N2 - 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.

AB - 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.

KW - AMPKα

KW - Arrestin beta 1

KW - Triple negative breast cancer

KW - miR-374a-5p

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U2 - 10.1016/j.canlet.2019.04.006

DO - 10.1016/j.canlet.2019.04.006

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SP - 224

EP - 233

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

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