Musashi RNA- binding protein 2 regulates estrogen receptor 1 function in breast cancer
Musashi RNA- binding protein 2 regulates estrogen receptor 1 function in breast cancer
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DOI：
10.1038/onc.2016.327
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发表时间：
2017-03-01
期刊：
影响因子：
8
通讯作者：
Park, Y-Y
中科院分区：
文献类型：
--
作者：
Kang, M-H;Jeong, K. J.;Park, Y-Y
Musashi RNA 结合蛋白 2 (MSI2) 在人类癌症中发挥重要作用。然而，MSI2 改变乳腺癌病理生理学的调节机制尚未明确。在这里，我们证明 MSI2 直接调节雌激素受体 1 (ESR1)，这是众所周知的治疗靶点，并已被证明可以反映乳腺癌的临床结果。基于基因表达数据分析，我们发现MSI2表达在雌激素受体（ER）阳性乳腺癌中高度富集，并且MSI2表达与ESR1表达显着相关，包括ESR1下游靶基因的表达。此外，MSI2 水平与临床结果相关。 MSI2 通过改变 ESR1 功能来影响乳腺癌细胞的生长。 MSI2 通过结合 ESR1 RNA 中的特定位点并增加 ESR1 蛋白稳定性来改变 ESR1。总而言之，我们的研究结果确定了 MSI2 作为 ESR1 上游调节因子的一种新调节机制，并揭示了 RNA 结合蛋白 MSI2 在乳腺癌中的临床相关性。
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.