WD40 repeat-containing 62 overexpression as a novel indicator of poor prognosis for human gastric cancer
WD40 repeat-containing 62 overexpression as a novel indicator of poor prognosis for human gastric cancer
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含有WD40重复序列的62过表达作为人类胃癌不良预后的新指标
DOI：
10.1016/j.ejca.2013.07.015
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发表时间：
2013-11-01
影响因子：
8.4
通讯作者：
Shen, Hong
中科院分区：
文献类型：
--
作者：
Zeng, Shan;Tao, Yiming;Shen, Hong
目的：WD 40 repeat-containing 62（WDR 62）是一个与细胞周期和增殖相关的中心体相关基因。然而，WDR 62在人类恶性肿瘤中的作用仍然未知。方法：采用定量逆转录-聚合酶链反应（qRT-PCR）、免疫组化和Western blotting方法检测372例胃癌组织和8株胃癌细胞系中WDR 62的表达。分析WDR 62表达与胃癌临床病理特征及预后的关系。结果：WDR 62在胃癌组织和胃癌细胞系中表达明显增高，与胃癌的分化程度和预后有关。GC多药耐药细胞中WDR 62表达增加。抑制WDR 62可显著抑制胃癌细胞的增殖，并使胃癌细胞阻滞于G2/M期。因此，WDR 62基因敲低可抑制裸鼠胃癌的发生。WDR 62对Akt/p38-丝裂原活化蛋白激酶（MAPK）/多药耐药基因1（MDR 1）表达的调节和激活参与了胃癌细胞的耐药性。结论：WDR 62可能是一种新的胃癌预后标志物和潜在的化疗靶点。(C)2013爱思唯尔有限公司保留所有权利。
Aim: WD40 repeat-containing 62 (WDR62) is a centrosome-associated gene involved in cell cycling and proliferation. However, the role of WDR62 in human malignancies remains unknown. The present study aimed to identify the role, if any, of WDR62 in the pathogenesis of human gastric cancer (GC).Methods: WDR62 expression in 372 cases of human GC and eight GC cell lines was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blotting. Correlations between WDR62 expression and clinicopathological characteristics, as well as GC prognosis were determined. WDR62 regulation of GC cell proliferation, invasion, migration and cell cycle distribution were studied both in vitro and in vivo.Results: WDR62 expression was significantly increased in GC tissues and cell lines and was associated with poor differentiation and prognosis of GC. WDR62 expression was elevated in GC multidrug resistant cells. Suppressing WDR62 significantly decreased cell proliferation and induced G2/M phase arrest of GC cells. Consistently, WDR62 knockdown inhibited gastric carcinogenesis in nudemice. Regulation of Akt/p38-mitogen-activated protein kinase (MAPK)/multidrug resistance gene 1 (MDR1) expression and activation byWDR62 contributed to the chemoresistance of GC cells. WDR62 over expresses in GC and the suppression of WDR 62 inhibits GC cell growth by inducing G2/M cell cycle arrest.Conclusion: WDR62 may be a novel prognostic marker and a potential chemotherapy target for GC. (C) 2013 Elsevier Ltd. All rights reserved.