Basic Research - Cancer(구연) (E-005)

BIRC5의 후성유전학적 조절을 통한 신세포암의 세포사멸 유도
¹한양대학교 의과대학 비뇨의학과 ²한양대학교 의생명공학전문대학원 임상의과학과
홍성휘¹, 장은비¹², 황현지¹², 이지영¹, 박성열¹, 문홍상¹, 윤영은¹
Renal cell carcinoma (RCC) is the most common type of kidney cancer accounting for approximately 85% of cases and is heterogeneous cancer including more than 20 subtypes. Because ccRCC accounts for more than 75% of RCC, most RCC studies were focused on the treatment and diagnosis of ccRCC. pRCC and chRCC have been relatively less studied, so we conducted this research to identify an epigenetic target for all subtype RCC treatment.

We analyzed the TCGA database of RCCs to find genetic target of all subtype RCCs. To investigate YM155 effect as a BIRC5 inhibitor in RCC, we conducted loss of function study in ccRCC (Caki1, 786-O, A498) and pRCC (Caki2, ACHN) cell lines. Based on the H3K27Ac, as an active enhancer mark, is enriched in the BIRC5 promoter, we explored the epigenetic mechanism for YM155. xenograft animal models were used to assess the efficacy of YM155, and YM155 was administered i.p. 3 times/week for 4 weeks.

In the analysis of the TCGA database, we discovered BIRC5, one of the IAPs family, as a key oncogene for RCCs. In both in vitro and in vivo experiments, the anti-tumor effect of YM155 was confirmed. In ChIP assay, H3K27Ac was decreased, while H3K27me3, which is a repressive promoter marker, was increased by YM155. Also, we indicated that level of BIRC5 is closely related with EMT markers via TCGA data.

This study suggested BIRC5 as a key gene that can target pRCC and ccRCC, and showed that anti-tumor effect and epigenetic switching mechanism of YM155 through in vitro and vivo. Furthermore, we believe that YM155 might be used to therapy of all subtype RCC.
keywords : RCC, BIRC5, Epigenetic switch