AUA 2018: Estrogen Receptor β Promotes Renal Cell Carcinoma Progression via Regulating LncRNA HOTAIR-miR-138/200c/204/217 Associated CeRNA Network

San Francisco, CA USA (UroToday.com)The relationship between the estrogen receptor and many known hormone-sensitive tumors has been identified, but the relationship of that and renal tumors has not been clearly observed. This clinical study presented by Jie Ding, MD, a urology specialist of the University of Rochester Medical Center, composed of the effect of over expressions and knockout of the estrogen receptor beta and the survival rate of patients with RCC. Although there was already identification between the regulatory relationship between the alpha and beta receptor, Dr. Ding’s team found a prevalent outcome of changes in expression of the estrogen receptor β. To observe the outcome of the true effect of the estrogen receptor β, specific markers were analyzed within the ERβ-HOTAIR-ceRNA axis. Determining the specific markers may help profile RCC progression and develop unique therapies to prevent further onset of the cancer.

To determine the relationship between the estrogen receptor β and the long-noncoding RNA, HOTAIR, in vitro and in vivo experiments were carried out and observed. Data for RNA was taken from The Cancer Genome Atlas, for a total of 537 patients with RCC. Results were also monitored in female mice and tumor progression was analyzed every two weeks using an in vivo imaging system. The estrogen receptor β was knocked-down and over-expressed and other markers were identified and analyzed. Other molecules within the pathway were also observed and compared to control patients. Significant differences in level of expression and onset of tumor progression were recorded and measured.

Analyzing the results of this study, Dr. Ding and the research team found a negative relationship between the estrogen receptor β and the likelihood of survival from RCC. Although there is already a negative relationship with the receptor, they found a significant decrease in survival rate when the estrogen receptor β was over expressed in the mice. When stimulating the mice with 17β-estradiol, they found that HOTAIR expression was altered and function increased by the antagonization of various microRNAs. Although the main catalyst for the change in RCC proliferation was caused by the estrogen receptor β, the LncRNA, HOITAR, also played a part in promoting RCC by modulation of the estrogen receptor β.

In conclusion, the results obtained in vitro and in vivo experiments suggested a relationship between the estrogen receptor β and the promotion of ccRCC. The decreased survival rate stimulated by the increased expression of the estrogen receptor β was also negatively affected by regulation of the long non-coding RNA, HOITAR, by suppressing various microRNAs within the tumor pathway. This study shows promising evidence to further investigate therapies that can focus on these markers to possibly predict and lower progression of ccRCC. Dr. Ding also brought up related studies for other types of cancers, such as breast and bladder cancers, that show promising results, and indicated another article being released in June regarding future analysis of this topic.

Presented by: Jie Ding, MD

Written by: Sherry Lu, Department of Urology, University of California-Irvine at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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