ER beta-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

作者：Han Zhenwei; Zhang Yong; Sun Yin; Chen Jiaqi; Chang Chawnshang; Wang Xiaolu; Yeh Shuyuan

来源：Cancer Research, 2018, 78(10): 2550-2563.

DOI：10.1158/0008-5472CAN-17-1575

Early studies have indicated that estrogen receptor beta (ERbeta) can influence the progression of clear cell renal cell carcinoma (ccRCC). Here, we report the mechanistic details of ERbeta-mediated progression of ccRCC. ERbeta increased ccRCC cell invasion via suppression of circular RNA ATP2B1 (circATP2B1) expression by binding directly to the 5' promoter region of its host gene ATPase plasma membrane Ca2(+) transporting 1 (ATP2B1). ERbeta-suppressed circATP2B1 then led to reduced miR-204-3p, which increased fibronectin 1 (FN1) expression and enhanced ccRCC cell invasion. Targeting ERbeta with shRNA suppressed ccRCC metastasis in a murine model of RCC; adding circATP2B1 shRNA partly reversed this effect. Consistent with these experimental results, ccRCC patient survival data from The Cancer Genome Atlas indicated that a patient with higher ERbeta and FN1 expression had worse overall survival and a patient with higher miR-204-3p expression had significantly better overall survival. Together, these results suggest that ERbeta promotes ccRCC cell invasion by altering the ERbeta/circATP2B1/miR-204-3p/FN1 axis and that therapeutic targeting of this newly identified pathway may better prevent ccRCC progression.Significance: These results identify an ERbeta/circATP2B1/miR-204-3p/FN1 signaling axis in RCC, suggesting ERbeta and circular RNA ATP2B1 as prognostic biomarkers for this disease. Cancer Res; 78(10); 2550-63.

• 出版日期2018-5-15