Original Articles
Liangsong Zhu, Jianfeng Wang, Wen Kong, Jiwei Huang, Baijun Dong, Yiran Huang, Wei Xue, Jin Zhang. LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling[J]. Acta Pharmaceutica Sinica B, 2019, 9(2): 324-334

LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling
Liangsong Zhu, Jianfeng Wang, Wen Kong, Jiwei Huang, Baijun Dong, Yiran Huang, Wei Xue, Jin Zhang
Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China
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 (P=0.006), especially 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 show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the CDKN1A 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.
Key words:    Clear cell renal cell carcinoma    LSD1    Prognosis    Proliferation    P21   
Received: 2018-06-06     Revised: 2018-08-23
DOI: 10.1016/j.apsb.2018.10.006
Funds: This study was supported by the National Nature Science Foundation of China (21472208 and 81625022).We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Corresponding author: Wei Xue, Jin Zhang     Email:uroxuewei@163.com;med-zhangjin@vip.sina.com
Author description:
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Liangsong Zhu
Jianfeng Wang
Wen Kong
Jiwei Huang
Baijun Dong
Yiran Huang
Wei Xue
Jin Zhang

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