ESRRA promotes gastric cancer development by regulating the CDC25C/CDK1/CyclinB1 pathway via DSN1.
ESRRA promotes gastric cancer development by regulating the CDC25C/CDK1/CyclinB1 pathway via DSN1.
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DOI：
10.7150/ijbs.57623
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发表时间：
2021
影响因子：
9.2
通讯作者：
Dong P
中科院分区：
文献类型：
--
作者：
Li FN;Zhang QY;Li O;Liu SL;Yang ZY;Pan LJ;Zhao C;Gong W;Shu YJ;Dong P
背景：雌激素相关受体-α （estrogen -相关receptor-α， ESRRA）是一种孤儿核受体，在旺盛代谢器官中高表达，并作为转录因子。在许多恶性肿瘤中均有高表达，但在脂质代谢紊乱较为常见的胃癌中未见相关研究。方法：采用Kaplan-Meier图分析ESRRA表达与患者预后的关系。实时荧光定量PCR检测ESRRA的表达水平。western-blot和免疫组化检测蛋白表达水平。流式细胞术检测细胞周期和凋亡。采用RNA-seq、生物信息学分析、双荧光素酶分析和ChIP分析预测和验证ESRRA的靶基因和结合基序。我们的研究还引入了动物模型。结果：ESRRA在胃癌细胞系中的表达明显升高，且高水平的ESRRA与预后不良相关。ESRRA沉默降低了GC细胞的活力、迁移和侵袭能力。其下游基因DSN1被RNA-seq发现，并被随后的生物信息学分析、双荧光素酶和ChIP实验证实。Western-blot结果显示，ESRRA沉默引起的G2M阻滞是通过CDC25C-CDK1-Cyclin B1途径实现的。结论：ESRRA/DSN1/CDC25C-CDK1-Cyclin B1在胃癌发生发展中起重要作用。ESRRA可能是胃癌的潜在靶标和预后指标。
Background: Estrogen-related receptor-α (ESRRA) is an orphan nuclear receptor, expressing at high level in exuberant metabolism organs and acting as transcription factor. High expression was found in many malignances but no research was done in gastric cancer (GC), where lipid metabolism disorder is common. Methods: Kaplan-Meier plot was utilized to find the relationship between ESRRA expression and patients' prognoses. The expression level of ESRRA was measured by real-time PCR. The protein expression levels were tested with western-blot and immunohistochemistry. Cell cycle and apoptosis was identified with flow cytometry. RNA-seq, bioinformatics analysis, dual-luciferase assay and ChIP assay were used to predict and validate ESRRA's target gene and binding motif. Animal models were also introduced in our study. Results: ESRRA expression is notably higher in GC cell lines and high ESRRA levels are correlated to poor prognoses. ESRRA silencing decreased GC cell viability, migration, and invasion capacities. Its downstream gene DSN1 was spotted by RNA-seq and confirmed by later bioinformatics analyses, dual-luciferase, and ChIP assays. Western-blot showed G2M arrest caused by ESRRA silencing was via CDC25C-CDK1-Cyclin B1 pathway. Conclusion: ESRRA/DSN1/CDC25C-CDK1-Cyclin B1 is of great importance in GC development. ESRRA could be a potential target as well as prognostic marker in GC.
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影响因子：
--
作者：
Chuang TP;Wang JY;Jao SW;Wu CC;Chen JH;Hsiao KH;Lin CY;Chen SH;Su SY;Chen YJ;Chen YT;Wu DC;Li LH
通讯作者：
Li LH
cyclin B1和CDC25与多倍体巨癌细胞形成相关的亚细胞定位及其临床病理意义
影响因子：
5
作者：
Fei, Fei;Qu, Jie;Zhang, Shiwu
通讯作者：
Zhang, Shiwu
影响因子：
15.9
作者：
Piyarathna, Danthasinghe Waduge Badrajee;Balasubramanian, Akhila;Sreekumar, Arun
通讯作者：
Sreekumar, Arun
DOI：
10.1073/pnas.1120968109
发表时间：
2012-06-05
影响因子：
11.1
作者：
Samel, Anke;Cuomo, Alessandro;Ehrenhofer-Murray, Ann E.
通讯作者：
Ehrenhofer-Murray, Ann E.
影响因子：
21.3
作者：
Jackman, M;Lindon, C;Pines, J
通讯作者：
Pines, J