Li Dezhi, Cheng Xianyi, Zheng Wei, Chen Junhui
Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, People's Republic of China.
Department of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen, Guangdong, People's Republic of China.
Cancer Manag Res. 2020 Jun 24;12:4923-4935. doi: 10.2147/CMAR.S250094. eCollection 2020.
Reprogramming of metabolic pathways is a hallmark of the pathological changes that occur in cancer cells. Under physiological conditions, glucosamine-6-phosphate isomerase 1 (GNPDA1) promotes the conversion of the hexosamine system to the glycolytic pathway and may, therefore, affect energy metabolism. Low expression of GNPDA1 has been reported in normal liver tissues, however, analysis of the hepatocellular carcinoma (HCC) database in The Cancer Genome Atlas (TCGA) revealed that GNPDA1 was highly expressed in HCC tissues. The purpose of this study was to explore the role of GNPDA1 in HCC.
We analyzed the expression of GNPDA1 in HCC tissues as well as the clinical outcomes of HCC patients with high or low expression of GNPDA1. Furthermore, the relationship between the expression of GNPDA1 and advanced tumor stage, TNM stage, grade, gender, or metastasis was assessed using high-throughput RNA sequencing data from TCGA HCC cohort and Kaplan-Meier survival analysis. The expression of GNPDA1 in HCC and normal liver cell lines was subsequently detected by qRT-PCR and Western blot analysis. Additionally, the effects of GNPDA1 knockdown in SMMC-7721 and Huh7 cell lines were examined. Cell proliferation, migration, invasion, and apoptosis following knockdown were investigated by the MTT assay and EdU, cell cycle, apoptosis, transwell, and wound healing analyses.
There was a significant association between high GNPDA1 expression and advanced tumor stage, TNM stage or grade, but not with gender. High GNPDA1 expression was associated with poor prognosis in patients with HCC. Furthermore, the MTT assay and EdU, cell cycle, apoptosis, wound healing, and transwell analyses revealed that GNPDA1 promoted the proliferation, migration, and invasion of HCC cells and inhibited apoptosis.
The results of this study suggest that GNPDA1 may serve as a novel prognostic biomarker and therapeutic target for HCC.
代谢途径的重编程是癌细胞发生的病理变化的一个标志。在生理条件下，6-磷酸葡糖胺异构酶1（GNPDA1）促进己糖胺系统向糖酵解途径的转化，因此可能影响能量代谢。据报道，正常肝组织中GNPDA1表达较低，然而，对癌症基因组图谱（TCGA）中肝细胞癌（HCC）数据库的分析显示，GNPDA1在HCC组织中高表达。本研究的目的是探讨GNPDA1在HCC中的作用。
我们分析了GNPDA1在HCC组织中的表达以及GNPDA1高表达或低表达的HCC患者的临床结局。此外，使用来自TCGA HCC队列的高通量RNA测序数据和Kaplan-Meier生存分析评估GNPDA1表达与肿瘤进展期、TNM分期、分级、性别或转移之间的关系。随后通过qRT-PCR和蛋白质印迹分析检测GNPDA1在HCC和正常肝细胞系中的表达。此外，还研究了GNPDA1在SMMC-7721和Huh7细胞系中的敲低效果。通过MTT法以及EdU、细胞周期、凋亡、transwell和伤口愈合分析研究敲低后细胞的增殖、迁移、侵袭和凋亡情况。
GNPDA1高表达与肿瘤进展期、TNM分期或分级显著相关，但与性别无关。GNPDA1高表达与HCC患者的不良预后相关。此外，MTT法以及EdU、细胞周期、凋亡、伤口愈合和transwell分析显示，GNPDA1促进HCC细胞的增殖、迁移和侵袭，并抑制凋亡。
本研究结果表明，GNPDA1可能作为HCC的一种新型预后生物标志物和治疗靶点。
