LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling
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 associate...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-03-01
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| Series: | Acta Pharmaceutica Sinica B |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383518304568 |
| _version_ | 1828883301854609408 |
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| author | Liangsong Zhu Jianfeng Wang Wen Kong Jiwei Huang Baijun Dong Yiran Huang Wei Xue Jin Zhang |
| author_facet | Liangsong Zhu Jianfeng Wang Wen Kong Jiwei Huang Baijun Dong Yiran Huang Wei Xue Jin Zhang |
| author_sort | Liangsong Zhu |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-13T10:46:04Z |
| format | Article |
| id | doaj.art-6abc699abc0449e880bb932dfa5c910b |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-13T10:46:04Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-6abc699abc0449e880bb932dfa5c910b2022-12-21T23:50:09ZengElsevierActa Pharmaceutica Sinica B2211-38352019-03-0192324334LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signalingLiangsong Zhu0Jianfeng Wang1Wen Kong2Jiwei Huang3Baijun Dong4Yiran Huang5Wei Xue6Jin Zhang7Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaDepartment of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaCorresponding authors.; Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaCorresponding authors.; Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, ChinaHistone 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, P21http://www.sciencedirect.com/science/article/pii/S2211383518304568 |
| spellingShingle | 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 Acta Pharmaceutica Sinica B |
| title | LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling |
| title_full | LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling |
| title_fullStr | LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling |
| title_full_unstemmed | LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling |
| title_short | LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating P21 signaling |
| title_sort | lsd1 inhibition suppresses the growth of clear cell renal cell carcinoma via upregulating p21 signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2211383518304568 |
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