{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhu L"],"funding":["National Nature Science Foundation of China"],"pagination":["324-334"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6437640"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(2)"],"pubmed_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 (<i>P</i>=0.006), especially tumor stage (<i>P</i>=0.017) and lymph node metastasis (<i>P</i>=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (<i>P</i><0.001) and recurrence-free survival (<i>P</i><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 <i>in vitro</i> and <i>in vivo</i>. Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the <i>CDKN1A</i> 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."],"journal":["Acta pharmaceutica Sinica. B"],"pubmed_title":["LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma <i>via</i> upregulating P21 signaling."],"pmcid":["PMC6437640"],"funding_grant_id":["81625022","21472208"],"pubmed_authors":["Xue W","Huang Y","Huang J","Zhang J","Zhu L","Wang J","Kong W","Dong B"],"additional_accession":[]},"is_claimable":false,"name":"LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma <i>via</i> upregulating P21 signaling.","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 (<i>P</i>=0.006), especially tumor stage (<i>P</i>=0.017) and lymph node metastasis (<i>P</i>=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (<i>P</i><0.001) and recurrence-free survival (<i>P</i><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 <i>in vitro</i> and <i>in vivo</i>. Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the <i>CDKN1A</i> 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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2025-04-18T20:26:22.88Z","creation":"2019-06-05T15:58:25Z"},"accession":"S-EPMC6437640","cross_references":{"pubmed":["30972280"],"doi":["10.1016/j.apsb.2018.10.006"]}}