Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53-dependent manner.
Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53-dependent manner.
复制标题
胃癌中升高的 PRC1 发挥致癌功能，并以 p53 依赖性方式成为胡椒长明的靶标。
DOI：
10.1111/jcmm.13063
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发表时间：
2017-07
影响因子：
5.3
通讯作者：
Zou X
中科院分区：
文献类型：
--
作者：
Zhang B;Shi X;Xu G;Kang W;Zhang W;Zhang S;Cao Y;Qian L;Zhan P;Yan H;To KF;Wang L;Zou X
胃癌是全球最常见的恶性肿瘤之一，也是中国癌症相关死亡的第二大常见原因。胞质分裂蛋白调节因子1（PRC 1）参与胞质分裂，在真核生物微管组织中起关键作用。本研究旨在分析PRC 1在胃癌中的表达，并探讨其在胃癌发生中的作用。通过qRT-PCR、Western blot和免疫组织化学评价PRC 1的表达。PRC 1的生物学功能通过CCK-8增殖试验、单层集落形成、异种移植裸鼠和通过AGS和HGC 27细胞中shRNA介导的敲低的细胞侵袭试验来确定。还使用双荧光素酶报告基因测定和ChIP-qPCR分析研究了piperlongumine对PRC 1表达的调节。PRC 1在原发性胃癌中上调。胃癌中PRC 1的过表达与疾病特异性生存率和总生存率相关。在AGS和HGC 27细胞系中PRC 1敲低抑制增殖，减少单层集落形成，抑制细胞侵袭和迁移能力，并诱导细胞周期停滞和凋亡。PRC 1的抑制也抑制了体内肿瘤生长。我们最终证实PRC 1是piperlongumine在胃癌中的一个新的下游靶标。我们的研究结果支持PRC 1在胃癌发生中的致癌作用。PRC 1可作为胃癌的预后标志物和潜在的治疗靶点。
Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer‐related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT‐PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK‐8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA‐mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual‐luciferase reporter assay and ChIP‐qPCR analysis. PRC1 was up‐regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease‐specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell‐cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma.