Estrogen Receptor Beta 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 (ER beta) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2/DAB2 interacting protein) signals and that blocking miR92a expression with an inhibitor could partially reverse ER beta-enhanced BCa cell growth and invasion. Further mechanism dissection found that ER beta 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 ER beta 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 ER ss/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 ER beta-mediated signal pathway to better suppress BCa progression.