Liu Chunhua, Shi Xuefei, Wang Li, Wu Ying, Jin Feiyan, Bai Cuiqing, Song Yong
Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China,
Tumour Biol. 2014 Jun;35(6):6073-82. doi: 10.1007/s13277-014-1804-5. Epub 2014 Mar 15.
The suppressor of zeste-12 protein (SUZ12), a core component of Polycomb repressive complex 2 (PRC2), is implicated in transcriptional silencing by generating di- and tri-methylation of lysine 27 on histone H3 (H3K27Me3). Although SUZ12 is known to be of great importance in several human cancer tumorigenesis, limited data are available on the expression profile and functional role of SUZ12 in non-small cell lung cancer (NSCLC). Here, we determined the expression level of SUZ12 in 40 paired clinical NSCLC tissues and adjacent normal tissues by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The results showed that SUZ12 was anomalously expressed in NSCLC tissues compared to adjacent noncancerous tissues (P<0.05) and was highly correlated to tumor size, lymph node metastasis, and clinical stages (P<0.05). Additionally, siRNA-mediated knockdown of SUZ12 could inhibit tumor cell growth, migration, and invasion, indicating that SUZ12 might function as an oncogene in NSCLC initiation and progression. Furthermore, we found that SUZ12 silencing significantly reduced the expression levels of transcription factor transcription factor E2F1 (E2F1) as well as potential metastasis promoters Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) and roundabout homolog 1 (ROBO1) through Western blot analysis. Altogether, we provide evidences suggesting that SUZ12 is an oncogene in NSCLC and can regulate NSCLC cells proliferation and metastasis partly via reducing E2F1, ROCK1, and ROBO1. Thus, SUZ12 may represent a new potential diagnostic marker for NSCLC and may be a novel therapeutic target for NSCLC intervention.
zeste-12蛋白抑制因子(SUZ12)是多梳抑制复合物2(PRC2)的核心成分,通过产生组蛋白H3赖氨酸27的二甲基化和三甲基化(H3K27Me3)参与转录沉默。尽管已知SUZ12在多种人类癌症的肿瘤发生中具有重要意义,但关于SUZ12在非小细胞肺癌(NSCLC)中的表达谱和功能作用的数据有限。在此,我们通过定量逆转录聚合酶链反应(qRT-PCR)测定了40对临床NSCLC组织和相邻正常组织中SUZ12的表达水平。结果显示与相邻的非癌组织相比,SUZ12在NSCLC组织中异常表达(P<0.05),并且与肿瘤大小、淋巴结转移和临床分期高度相关(P<0.05)。此外,siRNA介导的SUZ-12敲低可抑制肿瘤细胞的生长、迁移和侵袭,表明SUZ12可能在NSCLC的起始和进展中作为癌基因发挥作用。此外,我们通过蛋白质免疫印迹分析发现,SUZ12沉默显著降低了转录因子E2F1以及潜在转移促进因子Rho相关卷曲螺旋蛋白激酶1(ROCK1)和轴突导向分子1(ROBO1)的表达水平。总之,我们提供的证据表明,SUZ12是NSCLC中的一个癌基因,并且可以通过降低E2F1、ROCK1和ROBO1的表达来部分调节NSCLC细胞的增殖和转移。因此,SUZ12可能是NSCLC的一种新的潜在诊断标志物,并且可能是NSCLC干预的一个新的治疗靶点。