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Objective To investigate the role of phosphoglycerate kinase 1 (PGK1) in tumorigenesis and its potential post-translational modification sites were investigated by bioinformatics method and molecular biology experimental techniques, in order to provide evidence for PGK1 as a hepatocellular carcinoma ( HCC) diagnostic biomarker and therapeutic target. Methods From pan-cancer's point of view, 10 967 samples were obtained from the cancer genome database TCGAs, and the expression of PGK1 in different tumors was explored by using cBioPortal and UALCAN analysis tools; Focusing on HCC, the expression differences of PGK1 in hepatocellular carcinoma tumor tissues and normal tissues were further analyzed by using GEO database analysis, Real-time PCR, Western blotting and cell invasion assay;The String database was used to analyze the protein-protein interaction network and gene set enrichment analysis; The CSS-Palm database and bioinformatics method were used to predict protein post-translational modification sites on PGK1. Results The PGK1 gene was abnormally amplified and overexpressed in various solid tumors, including hepatocellular carcinoma, and overexpression of PGK1 was correlated with a poor prognosis in hepatocellular carcinoma. Multiple novel posttranslational modifications were existed on PGK1. Conclusion PGK1 is closely related to the occurrence and development of various cancers including HCC and glycolytic metabolism abnormalities. Epigenetic modifications can regulate PGK1 and affect its cellular function in HCC.
ABSTRACT
Phosphoglycerate kinase 1 (PGK1) is a key metabolic enzyme in the glycolysis pathway, which catalyzes the transfer of 1,3-bisphosphoglycerate (1,3-BPG) to 3-phosphoglycerate (3-PG) with ATP production. Over-expression of PGK1 has been observed in many types of malignance. Besides as a metabolic enzyme, PGK1 can also act as a protein kinase, which promotes the development and progression of tumors and correlates with chemoradiotherapy resistance and poor survival of cancer patients by regulating tumor cell metabolism. Functions of PGK1 were summarized in this article to provide theoretical basis for PGK1-targeting drug development.
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AIM:To study the expression and prognostic functions of phosphoglycerate kinase 1 ( PGK1) in prostate cancer. METHODS:The prostatic samples were collected from the patients with prostate cancer and benign pros-tatic hyperplasia (BPH) in TCM-Integrated Hospital of Southern Medical University from Jan 2013 to Dec 2013. The pro-tein expression of PGK1 in the prostate specimens was detected by immunohistochemical analysis and Western blot. Fur-thermore, the correlations of PGK1 expression with the clinicopathological features and prognosis of prostate cancer were al-so evaluate. RESULTS:The expression of PGK1 in the prostate specimens was significantly up-regulated compared with the BPH individuals. In addition, the expression of PGK1 was significantly correlated with the local infiltration, Gleason score, TNM grade, bone metastasis, and serum prostate-specific antigen (PSA) concentration. Finally, bone metastasis, serum PSA level and PGK1 expression were independent risk factors for prostate cancer illustrated by Cox analysis, and high expression of PGK1 was correlated with poor prognosis. CONCLUSION:PGK1 expression is an independent risk factor for prostate cancer, and it might act as a prognostic biomarker for prostate cancer.
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Objective@#To investigate the association between expression of phosphoglycerate kinase 1 (PGK1) in liver cancer tissue and prognosis, as well as its influence on metastasis and invasion of hepatocellular carcinoma (HCC) cells.@*Methods@#Overexpression and downregulated expression of PGK1 in HCC cells were mediated by lentivirus to establish hepatoma cell lines with different expression levels of PGK1. The Transwell chamber invasion assay, wound healing assay, and colony-forming assay were used to investigate the influence of PGK1 on metastasis, invasion, and proliferation of HCC cells. Immunohistochemistry was used to measure the expression of PGK1 in liver cancer tissue samples from 116 patients with hepatocellular carcinoma who underwent radical surgery, and the Kaplan-Meier method and the log-rank test were used to determine the association between PGK1 expression and prognosis of patients with liver cancer.@*Results@#HCCLM3 and MHCC97H HCC cells with high metastatic potential had significantly higher expression of PGK1 than Hep3B and Huh7 HCC cells with low metastatic potential. Downregulation of PGK1 expression significantly inhibited the migration (31.2% ± 2.4% vs 12.0% ± 1.3%, t = 21.57, P < 0.01), invasion (58 ± 11 vs 21 ± 8, t = 4.687, P < 0.05), and colony-forming ability (168.6 ± 15.1 vs 118.4 ± 8.1, t = 6.650, P < 0.05) of MHCC97H cells, while overexpression of PGK1 enhanced the migration (62.8% ± 4.4% vs 83.6% ± 6.1%, t = 20.56, P < 0.01), invasion (80 ± 12 vs 121 ± 15, t = 4.603, P < 0.05), and colony-forming ability (52.3 ± 8.6 vs 84.7 ± 9.0, t = 27.18, P < 0.01) of Hep3B cells. The high PGK1 expression group had significantly shorter median disease-free survival time and mean survival time than the low PGK1 expression group (22.00 ± 8.51 vs not reached, P < 0.05; 46.00 ± 16.87 vs not reached, P < 0.01).@*Conclusions@#PGK1 is involved in the regulation of metastasis and invasion of HCC cells and can promote the migration and invasion of HCC cells. Therefore, PGK1 may be an important predictor of prognosis and postoperative recurrence in patients with liver cancer.