Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 128, Issue 3, Pages 574-586Publisher
WILEY
DOI: 10.1002/ijc.25349
Keywords
LSD1; histone demethylase; epigenetics; bladder cancer; chromatin modification
Categories
Funding
- NIHR
- Cambridge Biomedical Research Centre
- MRC [G0900871] Funding Source: UKRI
- Cancer Research UK [19275] Funding Source: researchfish
- Medical Research Council [G0900871] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [22134008] Funding Source: KAKEN
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A number of histone demethylases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human disease like cancer have not been well understood. Here, we demonstrate important roles of lysine-specific demethylase 1 (LSD1) in human carcinogenesis. Expression levels of LSD1 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (p < 0.0001). cDNA microarray analysis also revealed its transactivation in lung and colorectal carcinomas. LSD1-specific small interfering RNAs significantly knocked down its expression and resulted in suppression of proliferation of various bladder and lung cancer cell lines. Concordantly, introduction of exogenous LSD1 expression promoted cell cycle progression of human embryonic kidney fibroblast cells. Expression profile analysis showed that LSD1 could affect the expression of genes involved in various chromatin-modifying pathways such as chromatin remodeling at centromere, centromeric heterochromatin formation and chromatin assembly, indicating its essential roles in carcinogenesis through chromatin modification.
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