G6PD upregulates Cyclin E1 and MMP9 to promote clear cell renal cell carcinoma progression.
G6PD upregulates Cyclin E1 and MMP9 to promote clear cell renal cell carcinoma progression.
复制标题
DOI：
10.7150/ijms.58902
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Zhang Q;Ni Y;Wang S;Agbana YL;Han Q;Liu W;Bai H;Yi Z;Yi X;Zhu Y;Sai B;Yang L;Shi Q;Kuang Y;Yang Z;Zhu Y
背景：透明细胞肾细胞癌（ccRCC）是一种转移率高、预后差的细胞代谢性疾病。我们之前的研究表明，葡萄糖-6-磷酸脱氢酶（G6PD）是戊糖磷酸途径的第一个限速酶，在 ccRCC 中高表达，并预测 ccRCC 患者的不良预后。本研究的目的是确认 G6PD 在 ccRCC 中的致癌作用，并揭示在 G6PD 介导的 ccRCC 进展中涉及 Cyclin E1 和 MMP9 的新机制。方法：采用实时RT-PCR、Western blot和免疫组化检测ccRCC中G6PD、Cyclin E1和MMP9的表达模式。使用TCGA数据集挖掘来确定Cyclin E1和MMP9与G6PD表达的相关性、ccRCC的临床病理特征与感兴趣的基因之间的关系以及ccRCC患者的预后。通过一系列体外细胞学功能测定，研究了 G6PD 在 ccRCC 进展中的作用以及 G6PD 对 Cyclin E1 和 MMP9 表达的调节作用。为了在体内验证这一机制，建立了异种移植小鼠模型。结果：G6PD、Cyclin E1和MMP9在ccRCC中过表达且呈正相关，且与ccRCC患者不良预后相关。此外，G6PD 改变了细胞周期动力学，促进细胞增殖，促进体外迁移，并增强体内 ccRCC 的发育，这更有可能是通过增强 Cyclin E1 和 MMP9 的表达来实现的。结论：这些发现表明 G6PD、Cyclin E1 和 MMP9 有助于 ccRCC 进展，可作为 ccRCC 治疗的新型生物标志物和潜在治疗靶点。
Background: Clear cell renal cell carcinoma (ccRCC) is a cell metabolic disease with high metastasis rate and poor prognosis. Our previous studies demonstrate that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in ccRCC and predicts poor outcomes of ccRCC patients. The aims of this study were to confirm the oncogenic role of G6PD in ccRCC and unravels novel mechanisms involving Cyclin E1 and MMP9 in G6PD-mediated ccRCC progression. Methods: Real-time RT-PCR, Western blot and immunohistochemistry were used to determine the expression patterns of G6PD, Cyclin E1 and MMP9 in ccRCC. TCGA dataset mining was used to identify Cyclin E1 and MMP9 correlations with G6PD expression, relationships between clinicopathological characteristics of ccRCC and the genes of interest, as well as the prognosis of ccRCC patients. The role of G6PD in ccRCC progression and the regulatory effect of G6PD on Cyclin E1 and MMP9 expression were investigated by using a series of cytological function assays in vitro. To verify this mechanism in vivo, xenografted mice models were established. Results: G6PD, Cyclin E1 and MMP9 were overexpressed and positively correlated in ccRCC, and they were associated with poor prognosis of ccRCC patients. Moreover, G6PD changed cell cycle dynamics, facilitated cells proliferation, promoted migration in vitro, and enhanced ccRCC development in vivo, more likely through enhancing Cyclin E1 and MMP9 expression. Conclusion: These findings present G6PD, Cyclin E1 and MMP9, which contribute to ccRCC progression, as novel biomarkers and potential therapeutic targets for ccRCC treatment.
登录
查看更多内容
影响因子：
5.9
作者：
LaMonte, Gregory;Tang, Xiaohu;Chi, Jen-Tsan
通讯作者：
Chi, Jen-Tsan
影响因子：
4.4
作者：
Bauernfeind AL;Babbitt CC
通讯作者：
Babbitt CC
RCC中泌尿肽组的肿瘤大小，阶段和等级改变。
影响因子：
7.4
作者：
Chinello C;Cazzaniga M;De Sio G;Smith AJ;Grasso A;Rocco B;Signorini S;Grasso M;Bosari S;Zoppis I;Mauri G;Magni F
通讯作者：
Magni F
影响因子：
10.1
作者：
Dannenmann, Stefanie R.;Hermanns, Thomas;van den Broek, Maries
通讯作者：
van den Broek, Maries
影响因子：
6.4
作者：
Hedberg, Y;Davoodi, E;Landberg, G
通讯作者：
Landberg, G