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.
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This research was supported by the Ministry of Education (NRF-2014R1A1A2053529 to Y-YP; NRF-2013R1A1A2064367 to M-HK) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI15C0972 to Y-YP).
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on the Oncogene website
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Kang, M., Jeong, K., Kim, W. et al. Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer. Oncogene 36, 1745–1752 (2017) doi:10.1038/onc.2016.327
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