Glucosamine-6-Phosphate Isomerase 1 Promotes Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma

Abstract

Dezhi Li,1 Xianyi Cheng,1 Wei Zheng,2 Junhui Chen1 1Intervention 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; 2Department of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Wei ZhengDepartment of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen International Biological Valley-Life Science Industrial Park, Shenzhen 518119, Guangdong, People’s Republic of ChinaTel [phone]Email [email protected] ChenIntervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Futian District, Shenzhen 518035, Guangdong, People’s Republic of ChinaTel [phone]Email [email protected]: 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.Patients and Methods: 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.Results: 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.Conclusion: The results of this study suggest that GNPDA1 may serve as a novel prognostic biomarker and therapeutic target for HCC.Keywords: hepatocellular carcinoma, glucosamine-6-phosphate isomerase 1, poor prognosis, reprogramming of metabolic pathways

Keywords

• hepatocellular carcinoma
• glucosamine-6-phosphate isomerase 1
• poor prognosis
• reprogramming of metabolic pathways