Presentation Authors: Jianfeng Wang*, Liangsong Zhu, Wen Kong, Jiwei Huang, Baijun Dong, Yiran Huang, Wei Xue, Jin Zhang, Shanghai, China, People's Republic of
Introduction: The purpose of this study was to investigate the role of Histone lysine specific dimethylase 1 (LSD1) in clear cell renal cell carcinoma (ccRCC) progression.
Methods: Immunohistochemistry was to investigate the expression pattern of LSD1 in 358 ccRCC tissues and explore itsprognostic function in RCC patients. Furthermore, the role of LSD1 in the growth of ccRCC in vitro and in vivo, used si-RNA knockdown and inhibited by a small molecule inhibitor SP2509.
Results: This study provided the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) clear cell renal cell carcinoma (ccRCC) patients. LSD1 expression level was associated with the progression of ccRCC, as indicated by TNM stage (p = 0.006), expecially tumor stage (p = 0.017) and lymph node metastasis (p = 0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (p < 0.001) and recurrence free survival (p < 0.001) of ccRCC patients. We further showed that LSD1 inhibition by siRNA knockdown or using a small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of the LSD1 decreased the H3K4 demethylation at CDKN1A gene promoter, which was associated with the p21 upregulation and cell cycle arrest at G1/S in ccRCC cells.
Conclusions: Together, our findings gained the new mechanistic insights into role of LSD in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.
Source of Funding: National Nature Science Foundation of China (21472208 and 81625022)