在表觀遺傳學(xué)里，賴氨酸特異性脫甲基酶1(LSD1)的生化特征已經(jīng)被鑒定,，但是它的失調(diào)與肺癌的相關(guān)性還不可知,。
近日，南京軍區(qū)總醫(yī)院肺癌綜合診治中心主任宋勇開(kāi)展了關(guān)于一項(xiàng)關(guān)于肺癌的研究,，該研究的目的在于評(píng)估非小細(xì)胞肺癌(NSCLC)患者LSD1表達(dá)的預(yù)后作用,，并明確它在肺癌增生、遷移及入侵等過(guò)程中的確切功能,。
來(lái)源于NSCLC患者外科切除標(biāo)本的LSD1蛋白水平通過(guò)免疫組化（immunohistochemistry）及蛋白印跡（Western blotting）被檢測(cè),。LSD1的mRNA水平則通過(guò)qRT-PCR測(cè)出。
LSD1的表達(dá)與臨床特征及預(yù)后的相關(guān)性由統(tǒng)計(jì)分析所確定,，細(xì)胞增殖率通過(guò)MTS分析及免疫熒光檢測(cè)被評(píng)估,。細(xì)胞遷移及入侵通過(guò)劃痕試驗(yàn)、基底膜侵襲實(shí)驗(yàn)及transwell侵襲小室試驗(yàn)檢測(cè),。
結(jié)果表明,，LSD1在肺癌組織中的表達(dá)高于正常肺組織，LSD1蛋白的過(guò)表達(dá)與NSCLC病人存活率的縮短有關(guān),。
LSD1主要定位于癌細(xì)胞核,，使用siRNA或者化學(xué)抑制劑（如巴吉林，一種單胺氧化酶抑制劑,，抗高血壓藥）來(lái)干擾LSD1,，抑制了A549, H460及293T細(xì)胞的增生、遷移及入侵,。
同時(shí)還發(fā)現(xiàn),，LSD1的過(guò)表達(dá)增強(qiáng)了細(xì)胞生長(zhǎng)，LSD1還被發(fā)現(xiàn)調(diào)節(jié)了肺癌細(xì)胞由上皮到間質(zhì)的轉(zhuǎn)移,。
LSD1的過(guò)表達(dá)與NSCLC的不良預(yù)后有關(guān),，促進(jìn)了腫瘤細(xì)胞的增生,、遷移和入侵。這些結(jié)果表明,，NSCLC是一種腫瘤促進(jìn)因子,，這也對(duì)NSCLC的治療提供了新的治療靶點(diǎn)。相關(guān)論文發(fā)表在4月6日的Plos One,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pone.0035065
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PMID:
Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer
Tangfeng Lv, Dongmei Yuan, Xiaohui Miao, Yanling Lv, Ping Zhan, Xiaokun Shen, Yong Song.
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.
