Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers
Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers
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DOI：
10.1002/ijc.25349
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发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
Hamamoto, Ryuji
中科院分区：
文献类型：
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作者：
Hayami, Shinya;Kelly, John D.;Hamamoto, Ryuji
许多组蛋白去甲基化酶已被鉴定和生物化学表征，但其功能障碍在人类疾病如癌症中的病理作用尚未得到很好的理解。在这里，我们证明了赖氨酸特异性脱甲基酶1（LSD 1）在人类癌症发生中的重要作用。与非肿瘤性膀胱组织相比，LSD 1在人膀胱癌中的表达水平显著升高（p < 0.0001）。cDNA微阵列分析也揭示了它在肺癌和结直肠癌中的反式激活。LSD1特异性小干扰RNA显著敲低其表达，并导致各种膀胱癌和肺癌细胞系的增殖抑制。一致地，外源性LSD 1表达的引入促进了人胚肾成纤维细胞的细胞周期进展。表达谱分析表明，LSD 1可影响多种染色质修饰途径中相关基因的表达，如着丝粒染色质重塑、着丝粒异染色质形成和染色质组装等，表明LSD 1通过染色质修饰在肿瘤发生中发挥重要作用。
A number of histone demethylases have been identified and biochemically characterized, but the pathological roles of their dysfunction in human disease like cancer have not been well understood. Here, we demonstrate important roles of lysine-specific demethylase 1 (LSD1) in human carcinogenesis. Expression levels of LSD1 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (p < 0.0001). cDNA microarray analysis also revealed its transactivation in lung and colorectal carcinomas. LSD1-specific small interfering RNAs significantly knocked down its expression and resulted in suppression of proliferation of various bladder and lung cancer cell lines. Concordantly, introduction of exogenous LSD1 expression promoted cell cycle progression of human embryonic kidney fibroblast cells. Expression profile analysis showed that LSD1 could affect the expression of genes involved in various chromatin-modifying pathways such as chromatin remodeling at centromere, centromeric heterochromatin formation and chromatin assembly, indicating its essential roles in carcinogenesis through chromatin modification.