Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer.
Musashi RNA-binding protein 2 (MSI2) has important roles in human cancer. However, the regulatory mechanisms by which MSI2 alters breast cancer pathophysiology have not been clearly identified. Here we demonstrate that MSI2 directly regulates estrogen receptor 1 (ESR1), which is a well-known therapeutic target and has been shown to reflect clinical outcomes in breast cancer. Based on gene expression data analysis, we found that MSI2 expression was highly enriched in estrogen receptor (ER)-positive breast cancer and that MSI2 expression was significantly correlated with ESR1 expression, including expression of ESR1 downstream target genes. In addition, MSI2 levels were associated with clinical outcomes. MSI2 influenced breast cancer cell growth by altering ESR1 function. MSI2 alters ESR1 by binding specific sites in ESR1 RNA and by increasing ESR1 protein stability. Taken together, our findings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance of the RNA-binding protein MSI2 in breast cancer.
Department of Convergence Medicine, Ulsan College of Medicine, Seoul, South Korea.
M-H
MH
Kang
Department of Systems Biology, MD Anderson Cancer Center, Houston, TX, USA.
K J
KJ
Jeong
Department of Surgery, Korea University, Guro Hospital, Seoul, South Korea.
W Y
WY
Kim
Department of Pathology, ASAN Medical Center, Seoul, South Korea.
H J
HJ
Lee
Department of Pathology, ASAN Medical Center, Seoul, South Korea.
G
G
Gong
Department of Medicine Engineering, College of Medical Sciences, Soon Chun Hyang University, Asan-si, South Korea.
N
N
Suh
MTA TTK Lendület Cancer Biomarker Research Group, Semmelweis University 2nd Department of Pediatrics, Budapest, Hungary.
B
B
Győrffy
Anging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
S
S
Kim
Department of Convergence Medicine, Ulsan College of Medicine, Seoul, South Korea.|ASAN Institute for Life Sciences, ASAN Medical Center, Seoul, South Korea.
S-Y
SY
Jeong
Department of Systems Biology, MD Anderson Cancer Center, Houston, TX, USA.
G B
GB
Mills
Department of Convergence Medicine, Ulsan College of Medicine, Seoul, South Korea.|ASAN Institute for Life Sciences, ASAN Medical Center, Seoul, South Korea.
Y-Y
YY
Park
D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D011485:Protein Binding; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D047628:Estrogen Receptor alpha; C438151:MSI2 protein, human; D016601:RNA-Binding Proteins