Functional characterization of and Pathway Dissection of Lysine-specific demethylase 1 (LSD1) in Nasopharyngeal carcinoma

• Main Authors: Chin Yi Young, 楊君怡
• Other Authors: H. C. Chen
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/20527465039290018554

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Aberrant epigenetic silencing of gene expression has been shown to contribute to tumorigenesis. Lysine-specific demethylase 1 (LSD1) was the first identified histone demethylase that plays an important role in chromatin remodeling and transcriptional regulation. To investigate the role of LSD1 in human malignancies, we analyzed the expression levels of LSD1 in public database and found that the expression levels of LSD1 were significantly elevated in several major types of human cancers. In-house immunohistochemical studies revealed that LSD1 proteins were mainly expressed in the nucleus and the expression levels were strongly elevated in tumor tissues of nasopharyngeal carcinoma (NPC). To explore the role of LSD1 in NPC tumorigenesis, we knockdowned the expression of LSD1 in NPC cells using small interfering RNA (siRNA) technology. siRNA-mediated silencing of LSD1 expression significantly suppressed the proliferation and colony formation of cultured NPC cells. Flow cytometric analysis revealed that silencing of LSD1 leaded to cell cycle arrest at the G0/G1 stage and also suppressed DNA synthesis. To identify potential targets mediating LSD1-induced cell cycle arrest, we analyzed the effect of LSD1 knockdown on the expression levels of several cell cycle-related genes listed in the KEGG pathway using real-time PCR technology. We found that silencing of LSD1 significantly altered the expression levels of several cell cycle-related genes. Chromatin immunoprecipitation analysis further confirmed that knockdown of LSD1 significantly altered the histone marks, including H3K4me2 and H3K9me2, in the promoter regions of CDC7 and MCM7 genes. Our results suggest that LSD1 may play an oncogenic role in NPC through epigenetic gene regulation.