Knockdown of SIRT1 Suppresses Bladder Cancer Cell Proliferation and Migration and Induces Cell Cycle Arrest and Antioxidant Response through FOXO3a-Mediated Pathways.
Knockdown of SIRT1 Suppresses Bladder Cancer Cell Proliferation and Migration and Induces Cell Cycle Arrest and Antioxidant Response through FOXO3a-Mediated Pathways.
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DOI：
10.1155/2017/3781904
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发表时间：
2017
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Hu Q;Wang G;Peng J;Qian G;Jiang W;Xie C;Xiao Y;Wang X
膀胱癌（BCa）是最常见的肿瘤之一，但其发病机制尚未完全阐明。我们的转录组分析表明，Sirtuins，过氧化物酶体激活受体（PPAR），细胞周期调控，活性氧（ROS）代谢，叉头盒O类（FOXO）信号通路在BCa中的密切联系。SIRT 1是Sirtuins的重要成员，在衰老和能量代谢中发挥重要作用，与多种代谢性疾病和肿瘤有关。我们观察到SIRT 1在BCa组织中在mRNA和蛋白水平上均上调。通过建立SIRT 1敲低的BCa细胞模型，我们的结果表明增殖和活力受到抑制。此外，迁移率也受到抑制，可能是通过减少上皮-间充质转化（EMT）。此外，细胞周期停滞被显著诱导，包括强烈减少的蛋白质参与（CDK 2/4/6）。此外，ROS的产生略有减少，伴随着增加的抗氧化酶和总/乙酰化FOXO 3a。与我们的Path-net分析一致，我们在SIRT 1敲低的BCa细胞中没有观察到细胞凋亡的显著改变。总之，我们的研究结果表明，SIRT 1缺陷BCa细胞可以抑制细胞活力，激活抗氧化反应和诱导细胞周期阻滞可能通过FOXO 3a相关的途径。
Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors. We observed that SIRT1 was upregulated in BCa tissues at both mRNA and protein levels. By establishing a SIRT1-knockdown BCa cell model, our results suggested that proliferation and viability were suppressed. Moreover, migration rate was inhibited as well, possibly via reduction of epithelial-mesenchymal transition (EMT). In addition, cell cycle arrest was significantly induced, consisting with strongly decreased proteins involved (CDK2/4/6). Furthermore, ROS production was slightly reduced, accompanied by increasing of antioxidant enzymes and total/acetylated FOXO3a. Consistently with our Path-net analysis, we observed no significant alteration of apoptosis in the SIRT1-knockdown BCa cells. Taken together, our results suggested that SIRT1 deficiency in BCa cells could suppress cell viability by activating antioxidant response and inducing cell cycle arrest possibly via FOXO3a-related pathways.
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影响因子：
3.3
作者：
Chung, Yul Ri;Kim, Hyojin;Ryu, Han Suk
通讯作者：
Ryu, Han Suk
DOI：
10.1016/j.numecd.2016.06.001
发表时间：
2016-11-01
影响因子：
3.9
作者：
Mariani, S.;Costantini, D.;Gnessi, L.
通讯作者：
Gnessi, L.
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
DOI：
10.18632/aging.100028
发表时间：
2009-03-02
期刊：
Aging
影响因子：
--
作者：
Allison SJ;Jiang M;Milner J
通讯作者：
Milner J