CBX7 regulates stem cell-like properties of gastric cancer cells via p16 and AKT-NF-κB-miR-21 pathways.
CBX7 regulates stem cell-like properties of gastric cancer cells via p16 and AKT-NF-κB-miR-21 pathways.
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DOI：
10.1186/s13045-018-0562-z
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发表时间：
2018-02-08
影响因子：
28.5
通讯作者：
Guo WJ
中科院分区：
文献类型：
--
作者：
Ni SJ;Zhao LQ;Wang XF;Wu ZH;Hua RX;Wan CH;Zhang JY;Zhang XW;Huang MZ;Gan L;Sun HL;Dimri GP;Guo WJ
染色体盒蛋白同源物7（CBX 7）是多梳组（PcG）蛋白家族的成员，参与细胞增殖和癌症进展的调节。PcG家族成员，如BMI、Mel-18和EZH 2，是多梳抑制复合物（PRC）的组成部分，并且已知可调节癌症干细胞（CSC）表型。然而，其他PRC的成分如CBX 7在CSC表型调节中的作用在很大程度上仍然难以捉摸。本研究旨在探讨CBX 7对胃癌干细胞样特性的调控作用及其机制。首先，使用球体形成、Western印迹和异种移植肿瘤测定来研究CBX 7在调节胃癌的干细胞样性质中的作用。接下来，采用RNA干扰和异位CBX 7表达来确定CBX 7对CSC标志物蛋白表达和CSC特征的影响。分析CBX 7及其下游靶点和干细胞标志物在胃干细胞球、常见癌细胞和胃癌组织中的表达。最后，探讨了CBX 7调控胃癌干细胞样特性的途径。我们发现CBX 7是多梳阻遏复合物1（PRC 1）的一个组成部分，通过激活AKT通路和下调p16在维持胃癌细胞干细胞样特性中起重要作用。斯皮尔曼等级相关分析显示胃癌组织中CBX 7与磷酸化AKT（pAKT）、干细胞标志物OCT-4和CD 133的表达呈正相关。此外，CBX 7通过激活AKT-NF-κB通路上调microRNA-21（miR-21），miR-21有助于CBX 7介导的CSC特征。CBX 7通过抑制p16和激活AKT-NF-κB-miR-21通路正向调节胃癌细胞的干细胞样特征。本文的在线版本（10.1186/s13045-018-0562-z）包含补充材料，可供授权用户使用。
Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs’ constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms. Firstly, the role of CBX7 in regulating stem cell-like properties of gastric cancer was investigated using sphere formation, Western blot, and xenograft tumor assays. Next, RNA interference and ectopic CBX7 expression were employed to determine the impact of CBX7 on the expression of CSC marker proteins and CSC characteristics. The expression of CBX7, its downstream targets, and stem cell markers were analyzed in gastric stem cell spheres, common cancer cells, and gastric cancer tissues. Finally, the pathways by which CBX7 regulates stem cell-like properties of gastric cancer were explored. We found that CBX7, a constituent of the polycomb repressive complex 1 (PRC1), plays an important role in maintaining stem cell-like characteristics of gastric cancer cells via the activation of AKT pathway and the downregulation of p16. Spearman rank correlation analysis showed positive correlations among the expression of CBX7 and phospho-AKT (pAKT), stem cell markers OCT-4, and CD133 in gastric cancer tissues. In addition, CBX7 was found to upregulate microRNA-21 (miR-21) via the activation of AKT-NF-κB pathway, and miR-21 contributes to CBX7-mediated CSC characteristics. CBX7 positively regulates stem cell-like characteristics of gastric cancer cells by inhibiting p16 and activating AKT-NF-κB-miR-21 pathway. The online version of this article (10.1186/s13045-018-0562-z) contains supplementary material, which is available to authorized users.
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DOI：
10.1186/bcr2106
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Grimshaw MJ;Cooper L;Papazisis K;Coleman JA;Bohnenkamp HR;Chiapero-Stanke L;Taylor-Papadimitriou J;Burchell JM
通讯作者：
Burchell JM
影响因子：
11.2
作者：
Datta, Sonal;Hoenerhoff, Mark J.;Dimri, Goberdhan P.
通讯作者：
Dimri, Goberdhan P.
DOI：
10.1016/s0140-6736(09)60617-6
发表时间：
2009-08-08
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hartgrink HH;Jansen EP;van Grieken NC;van de Velde CJ
通讯作者：
van de Velde CJ
影响因子：
8.4
作者：
Pallante, Pierlorenzo;Terracciano, Luigi;Tornillo, Luigi
通讯作者：
Tornillo, Luigi
影响因子：
29.4
作者：
Meng, Fanyin;Henson, Roger;Patel, Tushar
通讯作者：
Patel, Tushar