Basic Research - Cancer(구연) (E-016) 방광암에서 히스톤 디메틸라아제 KDM7A의 안드로겐 수용체 활성도 조절과, KDM7A 억제 물질을 통한 방광암 cisplatin 저항성 극복 가능성 규명 연구 1 서울대학교병원 비뇨의학과 2.카이스트 의과학대학원 서준교1, 이경화1, 김병창1, 정승환2, 정창욱1, 구자현1, 김현회1, 곽철1 Histone demethylase KDM7A regulates many biological processes including differentiation, development, and growth of several cancer cells. Here, we focused on the role of KDM7A in the bladder cancer cells, especially under the drug-resistant conditions. When the KDM7A gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown repressed AR activity in the bladder cancer cells through epigenetic regulation. When we developed cisplatin-resistant bladder cancer cell line, we found that the AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells showed decreased cell proliferation. In mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of bladder tumor. Finally, we observed that the KDM7A expression was upregulated in the patients with bladder cancer. These data suggested that histone demethylase KDM7A mediated the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in the patients with cisplatin-resistant bladder cancer. keywords : Bladder cancer; KDM7A; histone demethylase; TC-E 5002; androgen receptor; drug resistance