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 whichMSI2alters breast cancer pathophysiology have not been clearly identified. Here we demonstrate that MSI2 directly regulates estrogenreceptor 1 (ESR1), which is a well-known therapeutic target and has been shown to reflect clinical outcomes in breast cancer. Basedon gene expression data analysis, we found that MSI2 expression was highly enriched in estrogen receptor (ER)-positive breastcancer and that MSI2 expression was significantly correlated with ESR1 expression, including expression of ESR1 downstream targetgenes. In addition, MSI2 levels were associated with clinical outcomes. MSI2 influenced breast cancer cell growth by altering ESR1function. MSI2 alters ESR1 by binding specific sites in ESR1 RNA and by increasing ESR1 protein stability. Taken together, ourfindings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance ofthe RNA-binding protein MSI2 in breast cancer