Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking

Abstract

Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.

FOXK1 Participates in DNA Damage Response by Controlling 53BP1 Function

“…We also listed the top 30 significantly changed genes from each cluster ( Figure S4D ). For example, the top changed genes—ENO1, PGM1, and HIF1A from cluster 3, which function mainly in gluconeogenesis, canonical glycolysis, and the glycolytic process ( Choi et al, 2005 ; Ji et al, 2016 ; Jin et al, 2018 ) — were significantly downregulated in the FOXK1 KO and DKO groups. Conversely, several top changed genes—ERRFI1, ARHGAP29 and DUSP1 from cluster 4, which are involved mainly in intracellular signaling transduction and positive regulation of GTPase activity ( Calvisi et al, 2008 ; Post et al, 2013 ; Zhang and Vande Woude, 2007 )—were significantly upregulated in the FOXK1 KO and DKO groups ( Figure S4D ; Table S2 ).…”

Metastasis of Uveal Melanoma with Monosomy-3 Is Associated with a Less Glycogenetic Gene Expression Profile and the Dysregulation of Glycogen Storage

“…We initially identified n = 67 genes encoding proteins involved in glycogen synthesis or breakdown based on a literature and databank search using the platforms PubMed, Gene, OMIM, and UniProt ( Table S1 ) [ 15 , 16 , 22 , 23 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. We then calculated the median mRNA expression of these genes with regard to the monosomy-3 status with or without correction for the gene copy number.…”

Glucocorticoid Receptor ablation promotes cardiac regeneration by hampering cardiomyocyte terminal differentiation

“…Intriguingly, our data point at proteins of the I band and/or Z-disk, where the first step of sarcomere disassembly in proliferating cardiomyocytes has been previously reported 32 . Among downregulated I band genes in GR-cKO we observed PDLIM5 (PDZ and LIM domain protein 5, also known as Enigma Homolog -ENH), which plays a key role in Z-line structure 40 ; PGM1 (Phosphoglucomutase 1), an enzyme that is involved in energy metabolism, whose reduction lead to increased flow of glucose into glycolysis 41 , and may localize at the Z disk in stress conditions 42 ; ANK2 (Ankyrin-B), which is involved in calcium handling 43 ; RYR3 (Ryanodine Receptor type 3), which is mainly involved in calcium cycling in purkinje fibers 44,45 ;…”