Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer.
Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer.
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DOI：
10.1371/journal.pone.0035065
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Lv T;Yuan D;Miao X;Lv Y;Zhan P;Shen X;Song Y
赖氨酸特异性脱甲基酶1（LSD 1）已被鉴定并在表观遗传学中进行了生化表征，但其功能障碍在肺癌中的病理作用仍有待阐明。本研究的目的是评估LSD 1表达在非小细胞肺癌（NSCLC）患者中的预后意义，并确定其在肺癌增殖、迁移和侵袭中的确切作用。采用免疫组化和Western blotting方法检测NSCLC患者手术切除标本中LSD 1蛋白的表达。qRT-PCR检测LSD 1 mRNA水平。统计分析LSD 1表达与临床特征及预后的关系。MTS法和免疫荧光法检测细胞增殖率。划痕实验、基质胶实验和transwell侵袭实验检测细胞的迁移和侵袭能力。LSD 1在肺癌组织中的表达高于正常肺组织。我们的研究结果表明，LSD 1蛋白的过表达与NSCLC患者的总生存期较短相关。LSD 1主要定位于癌细胞核。使用siRNA或化学抑制剂帕吉林阻断LSD 1抑制A549、H460和293 T细胞的增殖、迁移和侵袭。同时，LSD 1的过表达促进细胞生长。最后，LSD 1被证明可以调节肺癌细胞中的上皮向间质转化。LSD 1过表达与NSCLC预后不良相关，并促进肿瘤细胞增殖、迁移和侵袭。这些结果表明，LSD 1是一种肿瘤促进因子，对NSCLC具有很好的治疗潜力。
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.
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