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

Dezhi Li; Xianyi Cheng; Wei Zheng; Junhui Chen

doi:10.2147/CMAR.S250094

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

Cancer Manag Res. 2020 Jun 24:12:4923-4935. doi: 10.2147/CMAR.S250094. eCollection 2020.

Authors

Dezhi Li¹, Xianyi Cheng¹, Wei Zheng², Junhui Chen¹

Affiliations

¹ 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.
² Department of Research and Development, Shenzhen Institute for Innovation and Translational Medicine, Shenzhen, Guangdong, People's Republic of China.

Abstract

Purpose: 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: glucosamine-6-phosphate isomerase 1; hepatocellular carcinoma; poor prognosis; reprogramming of metabolic pathways.

Grants and funding

This work was supported by Sanming Project of Medicine in Shenzhen (SZSM201612071), Shenzhen Basic Research Program under Grant (JCYJ20190809115811354), and Cell Technology Center and Transformation Base, Innovation Center of Guangdong-Hong Kong-Macao Greater Bay Area, Ministry of Science and Technology of China (YCZYPT [2018]03-1).