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(Department of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China) |
HONG Juan, WANG Dong-qing, YING Rui-geng, ZHAO Tian, ZHU Yan |
(Department of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China) |
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Abstract Objective: To investigate the expression of lysinespecific demethylse 1(LSD1) in nonsmall cell lung cancer (NSCLC) and its effect on cell proliferation and migration. Methods: The expression of LSD1 mRNA in 52 pairs of NSCLC tissues and adjacent tissues were determined by qRTPCR; and the relationship between LSD1 expression and clinical features were analyzed. Expression of LSD1 mRNA in NSCLC cell A549 and normal lung bronchial epithelial cells 16HBE were determined by qRTPCR. A549 cells were divided into 2 groups, transfected with LSD1 interfering RNA(siLSD1 group) and negative control RNA(control group), respectively. Cell proliferation, apoptosis and migration in the two groups were detected by MTT assay, clone formation assay, flow cytometry, and Transwell migration test. Epithelialmesenchymal transition related mRNA and protein expression levels were detected by qRTPCR and Western blotting. Results: Compared with adjacent tissues, LSD1 in NSCLC was significantly upregulated(t=2.861,P<0.05). The expression of LSD1 was correlated with TNM stage and lymph node metastasis in NSCLC patients (χ2=4.062, 6.047, P<0.05). There was no significant correlation between LSD1 expression and age, sex, smoking, tumor size and pathological type. Compared with the control group, siLSD group showed lower proliferation and metastasis, higher rate of cell apoptosis(t=3.618,P<0.05), upregulated expression of Ecadherin(t=5.607,P<0.05) and downregulated expression of vimentin(t=-6.628,P<0.05). Conclusion: The expression of LSD1 was upregulated in NSCLC. LSD1 might promote proliferation and metastasis by regulating EMT related gene.
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Received: 03 September 2017
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[1]Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgenreceptordependent transcription\[J\]. Nature, 2005, 437(7057): 436-439.[2]Amente S, Lania L, Majello B. The histone LSD1 demethylase in stemness and cancer transcription programs\[J\]. Biochim Biophys Acta, 2013, 1829(10): 981-986.[3]Kim J, Singh AK, Takata Y, et al. LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice\[J\]. Nat Commun, 2015, 6: 10116.[4]Wada T, Koyama D, Kikuchi J, et al. Overexpression of the shortest isoform of histone demethylase LSD1 primes hematopoietic stem cells for malignant transformation\[J\]. Blood, 2015, 125(24): 3731-3746.[5]Lei ZJ, Wang J, Xiao HL, et al. Lysinespecific demethylase 1 promotes the stemness and chemoresistance of Lgr5+ liver cancer initiating cells by suppressing negative regulators of βcatenin signaling\[J\]. Oncogene, 2015, 34(24): 3188-3198.[6]Chen L, Xu Y, Xu B, et al. Overexpression of lysinespecific demethylase 1 predicts tumor progression and poor prognosis in human esophageal cancer\[J\]. Int J Clin Exp Pathol, 2014, 7(12): 8929-8934.[7]Nagasawa S, Sedukhina AS, Nakagawa Y, et al. LSD1 overexpression is associated with poor prognosis in basallike breast cancer, and sensitivity to PARP inhibition\[J\]. PLoS One, 2015, 10(2): e118002.[8]Ketscher A, Jilg CA, Willmann D, et al. LSD1 controls metastasis of androgenindependent prostate cancer cells through PXN and LPAR6\[J\]. Oncogenesis, 2014, 3: e120.[9]Lynch JT, Harris WJ, Somervaille TC. LSD1 inhibition: a therapeutic strategy in cancer?\[J\]. Expert Opin Ther Targets, 2012, 16(12): 1239-1249.[10]Chen Y, Jie W, Yan W, et al. Lysinespecific histone demethylase 1 (LSD1): A potential molecular target for tumor therapy\[J\]. Crit Rev Eukaryot Gene Expr, 2012, 22(1): 53-59.[11]Wang M, Liu X, Guo J, et al. Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo\[J\]. Biochem Biophys Res Commun, 2015, 467(2): 310-315.[12]朱继云,汪慧访,邱江锋. 上皮—间质转化在肿瘤转移中的作用\[J\]. 中国生物化学与分子生物学学报,2014,30(12):1169-1175.[13]Shao G, Wang J, Li Y, et al. Lysinespecific demethylase 1 mediates epidermal growth factor signaling to promote cell migration in ovarian cancer cells\[J\]. Sci Rep, 2015, 5: 15344.[14]Kosumi K, Baba Y, Sakamoto A, et al. Lysinespecific demethylase1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer\[J\]. Int J Cancer, 2016, 138(2): 428-439.[15]董奇,丁杰. LSD1与肿瘤转移的研究进展\[J\]. 广东医学,2016,37(14): 2211-2213. |
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