Lysine-specific demethylase 1 promotes tumorigenesis and predicts prognosis in gallbladder cancer

Gallbladder Cancer (GBC), characterized by invasive growth and infiltrative dissemination, is difficult to diagnose and has poor prognosis. Emerging evidence demonstrates that Lysine-Specific Demethylase 1 (LSD1) has important roles in carcinogenesis, proliferation and metastasis. We studied the rol...

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Bibliographic Details
Published in:Oncotarget 2015-10, Vol.6 (32), p.33065-33076
Main Authors: Lian, Shi Xian, Shao, Ye Bo, Liu, Hou Bao, He, Jun Yi, Lu, Wei Qi, Zhang, Yong, Jiang, Ying, Zhu, Jun
Format: Article
Language:English
Subjects:
Animals
Carcinogenesis - genetics
Carcinogenesis - metabolism
Cell Line, Tumor
Cell Proliferation - physiology
Down-Regulation
Epithelial-Mesenchymal Transition
Gallbladder Neoplasms - enzymology
Gallbladder Neoplasms - genetics
Gallbladder Neoplasms - pathology
Gene Knockdown Techniques
Heterografts
Histone Demethylases - genetics
Histone Demethylases - metabolism
Humans
Male
Mice
Mice, Nude
Predictive Value of Tests
Prognosis
Research Paper
Up-Regulation
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Summary:Gallbladder Cancer (GBC), characterized by invasive growth and infiltrative dissemination, is difficult to diagnose and has poor prognosis. Emerging evidence demonstrates that Lysine-Specific Demethylase 1 (LSD1) has important roles in carcinogenesis, proliferation and metastasis. We studied the roles and molecular mechanisms of LSD1 in GBC. We examined LSD1 expression in 109 paired samples of GBC and normal gallbladder tissues. We found GBC tissues had upregulated LSD1 compared with normal gallbladder tissues (P = 0.003), and its high expression was associated with tumor-node-metastasis stage (P < 0.0001), Nevin's stage (P = 0.0093) and distant metastases (P = 0.0070). We found positive correlations between LSD1 expression and other proteins: epithelial-mesenchymal transition markers, C-myc and cyclin-related proteins. Inhibiting LSD1 expression in vitro impaired the proliferation and invasiveness of GBC cells and also downregulated c-myc expression and consequently inhibited GBC cell proliferation. LSD1 overexpression promotes GBC development and may be a predictor for a worsened prognosis. LSD1 may be a novel therapeutic target and prognostic tool for gallbladder cancer.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.5279