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Cancer Res. 2018 May 15;78(10):2550-2563. doi: 10.1158/0008-5472.CAN-17-1575. Epub 2018 Feb 28.

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

Author information

1
Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
2
George Whipple Lab for Cancer Research, Departments of Urology, Pathology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.
3
Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China. Shuyuan_Yeh@URMC.Rochester.edu wxl2106@126.com.
4
George Whipple Lab for Cancer Research, Departments of Urology, Pathology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York. Shuyuan_Yeh@URMC.Rochester.edu wxl2106@126.com.
#
Contributed equally

Abstract

Early studies have indicated that estrogen receptor beta (ERβ) can influence the progression of clear cell renal cell carcinoma (ccRCC). Here, we report the mechanistic details of ERβ-mediated progression of ccRCC. ERβ 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). ERβ-suppressed circATP2B1 then led to reduced miR-204-3p, which increased fibronectin 1 (FN1) expression and enhanced ccRCC cell invasion. Targeting ERβ 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 ERβ 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 ERβ promotes ccRCC cell invasion by altering the ERβ/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 ERβ/circATP2B1/miR-204-3p/FN1 signaling axis in RCC, suggesting ERβ and circular RNA ATP2B1 as prognostic biomarkers for this disease. Cancer Res; 78(10); 2550-63. ©2018 AACR.

PMID:
29490945
DOI:
10.1158/0008-5472.CAN-17-1575
[Indexed for MEDLINE]
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