Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer

• Published in: PloS one 2012-04, Vol.7 (4), p.e35065-e35065
• Main Authors: Lv, Tangfeng, Yuan, Dongmei, Miao, Xiaohui, Lv, Yanling, Zhan, Ping, Shen, Xiaokun, Song, Yong
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Androgens; Assaying; Bioassays; Biological assays; Biology; Biomarkers, Tumor - genetics; Breast cancer; Cancer; Cancer research; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cell cycle; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cell proliferation; Cell Proliferation - drug effects; Cell survival; DNA methylation; Enzymes; Epigenetic inheritance; Epigenetics; Epithelial-Mesenchymal Transition - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Health aspects; Histone Demethylases - antagonists & inhibitors; Histone Demethylases - genetics; Humans; Immunofluorescence; Immunohistochemistry; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lysine; Male; Medical research; Medicine; Mesenchyme; Metastasis; Middle Aged; mRNA; Neoplasm Invasiveness; Neuroblastoma; Non-small cell lung cancer; Non-small cell lung carcinoma; Nuclei; Nuclei (cytology); Overexpression; Pargyline; Pargyline - pharmacology; Patients; Phase transitions; Prognosis; Prostate cancer; RNA; RNA, Small Interfering - genetics; siRNA; Small cell lung cancer; Statistical analysis; Statistical methods; Studies; Survival Rate; T cells; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035065

Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. The protein levels of LSD1 in surgically resected samples from NSCLC patients were detected by immunohistochemistry or Western blotting. The mRNA levels of LSD1 were detected by qRT-PCR. The correlation of LSD1 expression with clinical characteristics and prognosis was determined by statistical analysis. Cell proliferation rate was assessed by MTS assay and immunofluorescence. Cell migration and invasion were detected by scratch test, matrigel assay and transwell invasion assay. LSD1 expression was higher in lung cancer tissue more than in normal lung tissue. Our results showed that over-expression of LSD1 protein were associated with shorter overall survival of NSCLC patients. LSD1 was localized mainly to the cancer cell nucleus. Interruption of LSD1 using siRNA or a chemical inhibitor, pargyline, suppressed proliferation, migration and invasion of A549, H460 and 293T cells. Meanwhile, over-expression of LSD1 enhanced cell growth. Finally, LSD1 was shown to regulate epithelial-to-mesenchymal transition in lung cancer cells. Over-expression of LSD1 was associated with poor prognosis in NSCLC, and promoted tumor cell proliferation, migration and invasion. These results suggest that LSD1 is a tumor-promoting factor with promising therapeutic potential for NSCLC.