Estrogen receptor β promotes bladder cancer growth and invasion via alteration of miR-92a/DAB2IP signals

Although early studies suggested that bladder cancer (BCa) is more prevalent in men than in women, muscle-invasive rates are higher in women than in men, suggesting that sex hormones might play important roles in different stages of BCa progression. In this work, we found that estrogen receptor beta (ERβ) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2⁄DAB2 interacting protein) signals and that blocking miR-92a expression with an inhibitor could partially reverse ERβ-enhanced BCa cell growth and invasion. Further mechanism dissection found that ERβ could increase miR-92a expression at the transcriptional level via binding to the estrogen-response-element (ERE) on the 5′ promoter region of its host gene C13orf25. The ERβ up-regulated miR-92a could decrease DAB2IP tumor suppressor expression via binding to the miR-92a binding site located on the DAB2IP 3′ UTR. Preclinical studies using an in vivo mouse model also confirmed that targeting this newly identified ERβ/miR-92a/DAB2IP signal pathway with small molecules could suppress BCa progression. Together, these results might aid in the development of new therapies via targeting of this ERβ-mediated signal pathway to better suppress BCa progression. Bladder cancer: stopping the spread Blocking the effects of the female hormone estrogen may increase the survival rate of women with bladder cancer (BCa). Although BCa is more common in men, tumors are more likely to invade neighboring tissues in women. Sex hormones and their receptors, which are known to affect progression of other cancers, may play a key role. A team led by Shuyuan Yeh at the University of Rochester Medical Center, USA, and Wang Long at Central South University, Changsha, China, investigated the role that estrogen receptor beta (ERβ) plays in BCa. They found that reducing ERβ levels made BCa cells less invasive. Further investigation revealed a way to block ERβ signaling, which made BCa tumors less likely to invade neighboring tissue in a mouse model. Understanding the ERβ signaling pathway may help to develop better treatments for BCa.