Guo Ting, Chen Tao, Gu Chao, Li Bin, Xu Congjian
Department of Gynaecology, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.
Department of Stem Cell and and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA, 02138, USA.
Tumour Biol. 2015 Sep;36(10):7649-58. doi: 10.1007/s13277-015-3463-6. Epub 2015 Apr 30.
We aimed to evaluate the role of glucose-6-phosphatase, catalytic subunit (G6PC) in ovarian cancer and to exploit its therapeutic potential. With reproduction of The Cancer Genome Atlas (TCGA) database, we studied expressions of genes in the glucose metabolism pathways in silico. The cBioPortal For Cancer Genomics was used to study the clinical, pathological and molecular profiles of G6PC. In vitro studies were performed to validate the function of G6PC and the effect of genetic and pharmaceutical G6PC inhibition. In 158 ovarian cancer (OvCa) patients with complete RNA-seq data, G6PC expression was increased in 27 patients (17 %). Both overall survival (OS) and disease-free period were significantly shorter in cases with increased G6PC level. Significantly decreased total and phosphorylated CDKN1B level was noted in OvCa with increased G6PC expression. Silenced G6PC in OvCa cells induced decreased cell proliferation, viability, invasiveness and anchorage-independent cell growth. G6PC silencing also induced enhanced cell cycle control proteins and restoration of CDKN1B level. Pharmaceutical inhibition of G6PC with specific compound showed similar effects to genetic silencing. G6PC played dual roles both in glucose metabolism and cell cycle control in OvCa, which potentiated it a promising therapeutic target.
我们旨在评估葡萄糖-6-磷酸酶催化亚基（G6PC）在卵巢癌中的作用，并挖掘其治疗潜力。通过重现癌症基因组图谱（TCGA）数据库，我们在计算机上研究了葡萄糖代谢途径中基因的表达情况。利用癌症基因组学的cBioPortal来研究G6PC的临床、病理和分子特征。进行体外研究以验证G6PC的功能以及基因和药物抑制G6PC的效果。在158例具有完整RNA测序数据的卵巢癌（OvCa）患者中，27例（17%）患者的G6PC表达升高。G6PC水平升高的病例中，总生存期（OS）和无病期均显著缩短。在G6PC表达升高的OvCa中，总CDKN1B水平和磷酸化CDKN1B水平显著降低。卵巢癌细胞中G6PC沉默导致细胞增殖、活力、侵袭性和非锚定依赖性细胞生长降低。G6PC沉默还诱导细胞周期调控蛋白增强以及CDKN1B水平恢复。用特定化合物对G6PC进行药物抑制显示出与基因沉默相似的效果。G6PC在卵巢癌的葡萄糖代谢和细胞周期调控中发挥双重作用，这使其成为一个有前景的治疗靶点。
