LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma upregulating P21 signaling.
10.1016/j.apsb.2018.10.006
- Author:
Liangsong ZHU
1
;
Jianfeng WANG
1
;
Wen KONG
1
;
Jiwei HUANG
1
;
Baijun DONG
1
;
Yiran HUANG
1
;
Wei XUE
1
;
Jin ZHANG
1
Author Information
1. Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
- Publication Type:Journal Article
- Keywords:
Clear cell renal cell carcinoma;
LSD1;
P21;
Prognosis;
Proliferation
- From:
Acta Pharmaceutica Sinica B
2019;9(2):324-334
- CountryChina
- Language:English
-
Abstract:
Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage (=0.006), especially tumor stage (=0.017) and lymph node metastasis (=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (<0.001) and recurrence-free survival (<0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC and . Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.
