Expression and clinical significance of phosphoglycerate kinase 1 in hepatocellular carcinoma based on bioinformatics methods

GUAN Cheng-Jian; YU Hua-Jing; ZHANG Xiao-Dong; RAO Quan; LIU Kun; WU Hong-Wei; WANG Dong; ZHANG Zhong-Tao; GUO Wei

doi:10.16098/j.issn.0529-1356.2022.06.008

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Acta Anatomica Sinica ›› 2022, Vol. 53 ›› Issue (6) : 744-753. DOI: 10.16098/j.issn.0529-1356.2022.06.008

Expression and clinical significance of phosphoglycerate kinase 1 in hepatocellular carcinoma based on bioinformatics methods

GUAN Cheng-jian YU Hua-jing ZHANG Xiao-dong RAO Quan ZHANG Wei-tao LIU Kun WU Hong-wei WANG Dong ZHANG Zhong-tao GUO Wei*

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Abstract

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 post-translational 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.

Key words

Phosphoglycerate kinase 1 / Cancer / / Hepatocellular carcinoma / / Bioinformatics / / Glycolysis / / Prognosis / / Western blotting / / Human

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GUAN Cheng-jian YU Hua-jing ZHANG Xiao-dong RAO Quan ZHANG Wei-tao LIU Kun WU Hong-wei WANG Dong ZHANG Zhong-tao GUO Wei. Expression and clinical significance of phosphoglycerate kinase 1 in hepatocellular carcinoma based on bioinformatics methods[J]. Acta Anatomica Sinica. 2022, 53(6): 744-753 https://doi.org/10.16098/j.issn.0529-1356.2022.06.008

References

［1］Villanueva A. Hepatocellular carcinoma ［J］. N Engl J Med, 2019, 380(15): 1450-1462.

［2］ForNer A, Reig M, Bruix J. Hepatocellular carcinoma ［J］. Lancet, 2018, 391(10127): 1301-1314.

［3］Lu HX, Wei DM, Feng ZhB, et al. Expression and clinical significance of EZH2 in hepatocellular carcinoma ［J］. Acta Anatomica Sinica, 2011, 42(1):75-79. (in Chinese)

陆海霞, 危丹明, 冯震博，等. EZH2在肝细胞癌中的表达及临床意义［J］.解剖学报，2011, 42(1): 75-79.

［4］Chen W. Cancer statistics: updated cancer burden in China ［J］. Chin J Cancer Res, 2015, 27(1): 1.

［5］Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma ［J］. Nat Rev Dis Primers, 2021, 7(1): 6.

［6］Schulze K, Imbeaud S, Letouze E, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets ［J］. Nat Genet, 2015, 47(5): 505-511.

［7］Bayo J, Fiore EJ, Dominguez LM, et al. A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets ［J］. J Hepatol, 2019, 71(1): 78-90.

［8］Gao Q, Zhu H, Dong L, et al. Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma ［J］. Cell, 2019, 179(2): 561-577.

［9］Li X, Jiang Y, Meisenhelder J, et al. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis ［J］. Mol Cell, 2016, 61(5): 705-719.

［10］Liang C, Shi S, Qin Y, et al. Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer ［J］. Gut, 2020, 69(5): 888-900.

［11］Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal ［J］. Sci Signal, 2013, 6(269): pl1.

［12］Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses ［J］. Neoplasia, 2017, 19(8): 649-658.

［13］Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets ［J］. Nucleic Acids Res, 2019, 47(D1): D607-D613.

［14］Ren J, Wen L, Gao X, et al. CSS-Palm 2.0: an updated software for palmitoylation sites prediction ［J］. Protein Eng Des Sel, 2008, 21(11): 639-644.

［15］Sonnhammer EL, Eddy SR, Durbin R. Pfam: a comprehensive database of protein domain families based on seed alignments ［J］. Proteins, 1997, 28(3): 405-420.

［16］Schultz J, Milpetz F, Bork P, et al. SMART, a simple modular architecture research tool: identification of signaling domains ［J］. Proc Natl Acad Sci USA, 1998, 95(11): 5857-5864.

［17］HU H, Zhu W, Qin J, et al. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis ［J］. Hepatology, 2017, 65(2): 515-528.

［18］Nie H, Ju H, Fan J, et al. O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth ［J］. Nat Commun, 2020, 11(1): 36.

［19］Hoekema A, Kastelein RA, Vasser M, et al. Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: experimental approach to study the role of biased codon usage in gene expression ［J］. Mol Cell Biol, 1987, 7(8): 2914-2924.

［20］Hansen RS, Gartler SM. 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5’ CpG island ［J］. Proc Natl Acad Sci USA, 1990, 87(11): 4174-4178.

［21］Gao S, Drouin R, Holmquist GP. DNA repair rates mapped along the human PGK1 gene at nucleotide resolution ［J］. Science, 1994, 263(5152): 1438-1440.

［22］Tan MJ, Luo H, Lee S, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification ［J］. Cell, 2011, 146(6): 1015-1027.

［23］Qian X, Li X, Shi Z, et al. PTEN suppresses glycolysis by dephosphorylating and inhibiting autophosphorylated PGK1 ［J］. Mol Cell, 2019, 76(3): 516-527.