Glycogen phosphorylase B promotes ovarian cancer progression via Wnt/ß-catenin signaling and is regulated by miR-133a-3p.

BACKGROUND: Ovarian cancer is one of the most common gynecologic cancers with high morbidity and mortality in women. Glycogen metabolism plays a critical role in cancer development and glycogen phosphorylase B (PYGB) has reported to be involved in various tumors. Here, we explored the role of PYGB in ovarian cancer. METHODS: PYGB mRNA expression were examined in ovarian cancer tissue and also analyzed using the dataset from The Cancer Genome Atlas cohort. Correlations between PYGB expression and prognosis of ovarian cancer patients were analyzed. PYGB was silenced to evaluate the ovarian cell proliferation, invasion and migration in vitro and tumorigenesis in vivo. MiR-133a-3p targeting PYGB was identified using online tools and confirmed with luciferase reporter experiment. MiR-133a-3p overexpression using miRNA mimics was conducted to evaluate its function on ovarian cancer cells. RESULTS: We showed that PYGB was upregulated in ovarian cancer tissue and high level of PYGB expression is markedly correlated with poor prognosis of ovarian cancer patients. PYGB knockdown significantly suppressed ovarian cancer cell proliferation, invasion and migration. Xenograft tumor formation further demonstrated that knockdown PYGB inhibited ovarian tumor development. Bioinformatics analysis revealed that PYGB regulated Wnt/ß-catenin signaling pathway in ovarian cancer cells. Mechanistically, miR-133a-3p directly bound to 3'-untranslated region of PYGB and overexpression miR-133a-3p suppressed proliferation, invasion and migration in ovarian cancer cells. CONCLUSION: Our data suggest that miR-133a-3p/PYGB/Wnt-ß-catenin axis plays a critical role in human ovarian cancer, which might serve as a promising therapeutic target of ovarian cancer treatment in the future.

Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia.

Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

Diagnostic accuracy of heart fatty acid binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) in diagnosis of acute myocardial infarction in patients with acute coronary syndrome.

INTRODUCTION: This study aimed to assess whether heart fatty acid-binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) could be used for the accurate diagnosis of acute myocardial infarction (AMI) in acute coronary syndrome (ACS) patients. MATERIALS AND METHODS: The study included 108 ACS patients admitted to a coronary unit within 3 h after chest pain onset. AMI was distinguished from unstable angina (UA) using a classical cardiac troponin I (cTnI) assay. H-FABP and GPBB were measured by ELISA on admission (0 h) and at 3, 6, 12, and 24 h after admission; their accuracy to diagnose AMI was assessed using statistical methods. RESULTS: From 92 patients with ACS; 71 had AMI. H-FABP and GPBB had higher peak value after 3 h from admission than cTnI (P = 0.001). Both markers normalized at 24 h. The area under the receiver operating characteristic curves was significantly greater for both markers in AMI patients than in UA patients at all time points tested, including admission (P < 0.001). At admission, the H-FABP (37%) and GPBB (40%) sensitivities were relatively low. They increased at 3 and 6 h after admission for both markers and decreased again after 24 h. It was 40% for H-FABP and approximately 2-times lower for GPBB (P < 0.01). In AMI patients, both biomarkers had similar specificities, positive- and negative-predictive values, positive and negative likelihood ratios, and risk ratios for AIM. CONCLUSION: H-FABP and GPBB can contribute to early AMI diagnosis and can distinguish AMI from UA.

Expression of the brain and muscle isoforms of glycogen phosphorylase in rat heart.

Heart glycogen represents a store of glucosyl residues which are mobilized by the catalysis of glycogen phosphorylase (GP) and are mainly destined to serve as substrates for the generation of ATP. The brain isoform of GP (GP BB) was studied in rat heart in comparison with the muscle isoform (GP MM) to find functional analogies to the brain. Western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed that at the protein level, but not at the mRNA level, the content of GP BB is similar in heart and brain. In contrast, GP MM is more abundant in the heart than in the brain. Immunocytochemically GP BB was colocalized with GP MM in cardiomyocytes. GP MM was also detected in interstitial cells identified as fibroblasts. The physiological role of co-expression of GP BB and GP MM in cardiomyocytes and in brain astrocytes is discussed in a comparative way.

Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies.

Isozyme-specific antibodies were raised against peptides from the low-homology regions of the sequences of rat glycogen phosphorylase BB and MM isozymes by immunization of rabbits and guinea pigs. Immunocytochemical double-labelling experiments on frozen sections of rat nervous tissues were performed to investigate the isozyme localization pattern. Astrocytes throughout the brain and spinal cord expressed both isozymes in perfect co-localization. Ependymal cells only expressed the BB isozyme. Most neurones were not immunoreactive. The rare neurones that contained glycogen phosphorylase only expressed the BB isozyme. Nearly all of these neurones formed part of the afferent somatosensory system. These findings stress the general importance of glycogen in neural energy metabolism and indicate a special role for the glycogen phosphorylase BB isozyme in neurones in the somatosensory system.

BGP expression in gastric biopsies may predict the development of new lesions after local treatment for early gastric cancer.

BACKGROUND: Our previous studies have demonstrated the significant role of the generative cells of intestinal metaplasia (IM) expressing brain (fetal)-type glycogen phosphorylase (BGP) (BGP-IM) as a premalignant lesion of intestinal-type adenocarcinoma. The aims of the present study were to investigate the incidence of BGP-IM in gastric biopsy specimens and to establish BGP-IM as a predictor of the coexistence of accessory carcinoma and/or metachronous cancers before and after local treatment for early gastric carcinoma. METHODS: We studied the incidence of BGP-IM in eight endoscopic biopsy specimens of methylene blue-positive mucosa of the stomach obtained from patients with multiple gastric carcinomas (n = 14), a single carcinoma (n = 25), and atrophic gastritis (n = 20). RESULTS: BGP positivity was 93.3% in the multiple carcinomas and 80.0% in the single carcinomas. The incidences of BGP-IM (mean percentage +/- SD) in the stomachs with multiple carcinomas, single carcinoma, and atrophic gastritis were 83.2% +/- 22.8%, 36.5% +/- 41.3%, and 7.1% +/- 18.0%, respectively. The incidence was significantly higher in the stomachs with multiple carcinomas than in those with a single carcinoma or those with atrophic gastritis (P < 0.001). CONCLUSION: It is suggested that the frequent appearance of BGP-IM reflects the high potential of carcinogenesis of intestinal-type gastric cancer, and that the involvement of BGP-IM in more than 50% of the eight biopsies may be a predictor of the coexistence of accessory and/or metachronous carcinoma before and after local treatment for early gastric carcinoma.