Cui Yingjun, Chen Jie, He Zhixian, Xiao Yongtao
Department of Surgery, Yantaishan Hospital, Yantai, China.
Cell Physiol Biochem. 2013;31(6):778-84. doi: 10.1159/000350095. Epub 2013 May 31.
BACKGROUND/AIMS: SUZ12 and EZH2 are two main components of polycomb repressive complex 2 (PRC2) that is known to be of great importance in tumorigenesis. EZH2 has been reported to play a vital role in pathogenesis of human cancer. However, whether SUZ12 has equivalent roles in tumorigenesis has not been demonstrated. Here, we investigated a possible role of SUZ12 for the proliferation of gastric cancer cells.
Western-blot analysis was used to detected the levels of SUZ12, H3K27me3, EZH2 and p27 in ten gastric cell lines. SUZ12 was depleted by RNA interference. Cell cycle was detected by flow cytometry. Luciferase assays was to analyze whether miR-200b directly regulate SUZ12.
We found that SUZ12 depletion mediated by RNA interference (RNAi) led to a reduction of gastric cell numbers and arrested the cell cycle at G1/S point. As an important G1/S phase inhibitory gene, p27 is re-induced to some extent by SUZ12 knockdown. Furthermore, we demonstrated that SUZ12 was directly downregulated by miR-200b.
We provide evidence suggesting that SUZ12 may be a potential therapeutic target for gastric cancer.
背景/目的:SUZ12和EZH2是多梳抑制复合物2(PRC2)的两个主要组成部分,已知其在肿瘤发生中具有重要意义。据报道,EZH2在人类癌症发病机制中起关键作用。然而,SUZ12在肿瘤发生中是否具有同等作用尚未得到证实。在此,我们研究了SUZ12在胃癌细胞增殖中的可能作用。
采用蛋白质免疫印迹分析检测十种胃癌细胞系中SUZ12、H3K27me3、EZH2和p27的水平。通过RNA干扰使SUZ12表达缺失。采用流式细胞术检测细胞周期。荧光素酶测定法用于分析miR-200b是否直接调控SUZ12。
我们发现,RNA干扰(RNAi)介导的SUZ12缺失导致胃癌细胞数量减少,并使细胞周期停滞在G1/S期。作为一个重要的G1/S期抑制基因,p27在一定程度上因SUZ12表达下调而重新诱导表达。此外,我们证明了miR-200b可直接下调SUZ12。
我们提供的证据表明,SUZ12可能是胃癌的一个潜在治疗靶点。