Alkylglycerone Phosphate Synthase Research Articles

The suppression of nuclear factor kappa B/microRNA 222 axis alleviates lipopolysaccharide-induced acute lung injury through increasing the alkylglyceronephosphate synthase expression

BackgroundAcute lung injury (ALI) is a serious and rapidly progressing pulmonary disorder with a high mortality rate. In this study, we aimed to investigate the relationship between miR-222 and NF-κB (p65) activation in ALI. MethodsALI was induced in mice using lipopolysaccharide (LPS). Lung tissues and bronchoalveolar lavage fluid were collected for analysis. MH-S cell lines were used as an ALI model. Various techniques including histopathology, molecular analysis, and cell culture assays were employed. ResultsIncreased miR-222 levels were observed in the LPS-induced ALI mouse model. ALI mice exhibited severe lung pathology, inflammatory cell infiltration, edema, elevated W/D ratio, MPO activity, and increased TNFα, IL1, and IL6 levels, which were reversed by miR-222 antagomir, confirming miR-222’s exacerbation of LPS-induced ALI. miR-222 directly targeted the 3’-UTR of alkylglyceronephosphate synthase (AGPS) mRNA, reducing its expression. AGPS is crucial for plasmalogen synthesis, which protects against oxidative stress. NF-κB (p-p65) levels were increased in ALI models, and LPS promoted the enrichment of the miR-222 promoter region, suggesting NF-κB (p65) involvement in miR-222 transcriptional regulation. The NF-κB/miR-222/AGPS axis played a significant role in ALI progression. ConclusionsThe present study indicates that NF-κB (p65) activates miR-222 transcription by enriching its promoter region, leading to increased miR-222 expression. Elevated miR-222 levels downregulate AGPS, thereby accelerating the progression of ALI. Targeting the NF-κB/miR-222/AGPS axis may hold promise as a therapeutic approach for ALI, although further research is needed to fully understand its significance.

The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression

Abnormalities in ether lipid metabolism as well as the formation of neutrophil extracellular traps have recently been recognized as detrimental factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here we show that the lipid metabolism-related gene enoyl-CoA δ-isomerase 2 (ECI2) plays a tumor-suppressor role in CRC and is negatively associated with poor prognosis in CRC patients. We mechanistically demonstrate that ECI2 reduces ether lipid-mediated Interleukin 8 (IL-8) expression leading to decreased neutrophil recruitment and neutrophil extracellular traps formation for colorectal cancer suppression. In particular, ECI2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS), the rate-limiting enzyme for ether lipid synthesis. These findings not only deepen our understanding of the role of metabolic reprogramming and neutrophil interactions in the progression of CRC, but also provide ideas for identifying potential diagnostic markers and therapeutic targets for CRC.

Endogenous ether lipids differentially promote tumor aggressiveness by regulating the SK3 channel

SK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells. Experiments revealed that the suppression of alkylglycerone phosphate synthase or plasmanylethanolamine desaturase 1, which are key enzymes for alkyl- and alkenyl-ether-lipid synthesis, respectively, decreased SK3 expression by increasing micro RNA (miR)-499 and miR-208 expression, leading to a decrease in SK3-dependent calcium entry, cell migration, and matrix metalloproteinase 9–dependent cell adhesion and invasion. We identified several ether lipids that promoted SK3 expression and found a differential role of alkyl- and alkenyl-ether lipids on SK3 activity. The expressions of alkylglycerone phosphate synthase, SK3, and miR were associated in clinical samples emphasizing the clinical consistency of our observations. To our knowledge, this is the first report showing that ether lipids differentially control tumor aggressiveness by regulating an ion channel. This insight provides new possibilities for therapeutic interventions, offering clinicians an opportunity to manipulate ion channel dysfunction by adjusting the composition of ether lipids.

A lipidome landscape of aging in mice.

Understanding the molecular mechanisms of aging is crucial for enhancing healthy longevity. We conducted untargeted lipidomics across 13 biological samples from mice at various life stages (2, 12, 19 and 24 months) to explore the potential link between aging and lipid metabolism, considering sex (male or female) and microbiome (specific pathogen-free or germ-free) dependencies. By analyzing 2,704 molecules from 109 lipid subclasses, we characterized common and tissue-specific lipidome alterations associated with aging. For example, the levels of bis(monoacylglycero)phosphate containing polyunsaturated fatty acids increased in various organs during aging, whereas the levels of other phospholipids containing saturated and monounsaturated fatty acids decreased. In addition, we discovered age-dependent sulfonolipid accumulation, absent in germ-free mice, correlating with Alistipes abundance determined by 16S ribosomal RNA gene amplicon sequencing. In the male kidney, glycolipids such as galactosylceramides, galabiosylceramides (Gal2Cer), trihexosylceramides (Hex3Cer), and mono- and digalactosyldiacylglycerols were detected, with two lipid classes-Gal2Cer and Hex3Cer-being significantly enriched in aged mice. Integrated analysis of the kidney transcriptome revealed uridine diphosphate galactosyltransferase 8A (UGT8a), alkylglycerone phosphate synthase and fatty acyl-coenzyme A reductase 1 as potential enzymes responsible for the male-specific glycolipid biosynthesis in vivo, which would be relevant to sex dependency in kidney diseases. Inhibiting UGT8 reduced the levels of these glycolipids and the expression of inflammatory cytokines in the kidney. Our study provides a valuable resource for clarifying potential links between lipid metabolism and aging.

Helicobacter pylori CagA-mediated ether lipid biosynthesis promotes ferroptosis susceptibility in gastric cancer

Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis. This susceptibility is mediated by activation of the MEK/ERK/SRF pathway. SRF is a crucial transcription factor that increases AGPS transcription by binding to the AGPS promoter region. Moreover, the results demonstrated that CagA-positive cells are more sensitive to apatinib than are CagA-negative cells, suggesting that detecting the H. pylori CagA status may aid patient stratification for treatment with apatinib.

Determination of the Possible Target Genes of Hepatoma-derived Growth Factor in Hepatoma Cells.

We identified a new growth factor, hepatoma-derived growth factor (HDGF), which is a presumed growth-stimulating factor of hepatocellular carcinoma (HCC). Recently, we identified two microRNAs (miR-6072 and miR-3137) induced by HDGF, which were also found to be associated with the prognosis of HCC patients. This study aimed to identify the target genes of these HDGF-related microRNAs. A public database was searched for candidate target genes of HDGF-related microRNAs. Using the microarray system, the genes whose expression changed in response to HDGF administration were determined. Finally, a public cancer genomics database was searched for genes that were induced by HDGF and associated with the prognosis of HCC. A total of 1,132 genes were identified as common target genes of the 2 HDGF-related microRNAs. Among these genes, a microarray system showed that the expression of 6 genes was increased (≥1.5-fold) or decreased (≤0.67-fold) after HDGF administration. Using a cancer genomics database, two of the six genes were found to be related to the prognosis of HCC. A high expression of alkylglycerone phosphate synthase (AGPS) was significantly associated with a poor survival (p=0.0025, 0.0063 and 0.0081 for the 1-, 3- and 5-year survival, respectively). A high expression of the shroom family member 4 (SHROOM4) gene was found to be significantly associated with a better survival (p=0.003, 0.0006 and 0.0006 for the 1-, 3- and 5-year survival, respectively). This study identified potential target genes of HDGF-related microRNAs that were associated with the prognosis of HCC.

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells.

Oxidative stress is closely linked to Alzheimer’s disease (AD), and is detected peripherally as well as in AD-vulnerable brain regions. Oxidative stress results from an imbalance between the generation and degradation of reactive oxidative species (ROS), leading to the oxidation of proteins, nucleic acids, and lipids. Extensive lipid changes have been found in post mortem AD brain tissue; these changes include the levels of total phospholipids, sphingomyelin, and ceramide, as well as plasmalogens, which are highly susceptible to oxidation because of their vinyl ether bond at the sn-1 position of the glycerol-backbone. Several lines of evidence indicate that a deficiency in the neurotropic vitamin B12 is linked with AD. In the present study, treatment of the neuroblastoma cell line SH-SY5Y with vitamin B12 resulted in elevated levels of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and plasmalogens. Vitamin B12 also protected plasmalogens from hydrogen peroxide (H2O2)-induced oxidative stress due to an elevated expression of the ROS-degrading enzymes superoxide-dismutase (SOD) and catalase (CAT). Furthermore, vitamin B12 elevates plasmalogen synthesis by increasing the expression of alkylglycerone phosphate synthase (AGPS) and choline phosphotransferase 1 (CHPT1) in SH-SY5Y cells exposed to H2O2-induced oxidative stress.

Transcriptome analysis of the gills of Eriocheir sinensis provide novel insights into the molecular mechanisms of the pH stress response

Eriocheir sinensis is an important economic species in China, which is easily affected by pH changes. However, the molecular mechanism of the pH stress response in E. sinensis is still unclear. Therefore, this study aimed to examine the molecular response mechanism of E. sinensis based on pH variation surveillance, histopathological evaluation and transcriptomic analyses. Firstly, pH variation surveillance showed that E. sinensis could actively regulate the pH of its environment. Meanwhile, the histopathological evaluation suggested that pH stress seriously damaged the gills, especially at high pH. Finally, transcriptome analysis showed that the expression of genes related to ion transport, immune stress, and energy metabolism significantly changed. Many genes played an important role in the pH response of E. sinensis, such as carbonic anhydrase (CA), mitochondrial proton/calcium exchanger protein (LETM1), recombinant sodium/hydrogen exchanger 3 (SLC9A3/NHE3), heat shock protein 90 alpha family class a member (HSP90A), alkylglycerone phosphate synthase (AGPS), succinate-CoA ligase ADP-forming subunit beta (LSC2), and superoxide dismutase (SOD). Our study revealed the molecular response mechanism of E. sinensis in response to pH stress, thus providing a basis for further research on the molecular mechanism of response to pH stress in aquatic animals.

Mass Spectrometry and Computer Simulation Predict the Interactions of AGPS and HNRNPK in Glioma.

Ether lipids are overexpressed in malignant tumor and play an important role in tumor process. Glioma is the most common malignant central nervous system tumor, and the content of ether lipids is higher than that of normal tissues. Alkylglycerone phosphate synthase (AGPS) is a key enzyme in the synthesis of ether esters and plays a vital role in maintaining the morphology and pathogenic properties of tumor cells. The cell proliferation and the content of tumor-related lipid such as monoalkylglycerol ether (MAGe), lysophosphatidic acid ether (LPAe), lysophosphatidylcholine ether (LPCe), lysophosphatidylethanolamine ether (LPEe), phosphatidyl inositol (PI), phosphatidylcholine (PC), and phosphatidylserine (PS) were suppressed after AGPS silencing in U251, H4, and TJ905 cells; however, heterogeneous nuclear ribonucleoprotein K (HNRNPK) could reverse the above phenomenon such as cellar proliferation and ether lipid secretion. We found that HNRNPK was the target protein of AGPS by coimmunoprecipitation and mass spectrometry assay and verified by western blot assay in U251 cells. It confirmed that AGPS and HNRNPK are coexpressed in the cellular nucleus by a confocal laser microscope. The main protein-protein interaction mechanism between AGPS and HNRNPK is hydrogen bond, conjugation bond, hydrophobic bond, and electrostatic force by computer simulation prediction.

NEAT1/hsa-miR-372–3p axis participates in rapamycin-induced lipid metabolic disorder

Rapamycin is a crucial immunosuppressive regimen for patients that have undergone liver transplantation (LT). However, one of the major side effects of rapamycin include metabolic disorders such as dyslipidemia, and the mechanism remains unknown. This study aims to explore the biomolecules that are responsible for rapamycin-induced dyslipidemia and the control strategies that can reverse the lipid metabolism disorder. In this study, data collected from LT patients, cell and mouse models treated with rapamycin were analyzed. Results showed an increase of triglycerides (TGs) induced by rapamycin. MicroRNAs (miRNAs) play important roles in many vital biological processes including TG metabolism. hsa-miR-372–3p was filtered using RNA sequencing and identified as a key regulator in rapamycin-induced TGs accumulation. Using bioinformatics and experimental analyses, target genes of hsa-miR-372–3p were predicted. These genes were alkylglycerone phosphate synthase (AGPS) and apolipoprotein C4 (APOC4), which are reported to be involved in TG metabolism. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was also identified as an upstream regulatory factor of hsa-miR-372–3p. From the results of this study, NEAT1/hsa-miR-372–3p/AGPS/APOC4 axis plays a vital role in rapamycin-disruption of lipid homeostasis. Therefore, targeting this axis is a potential therapeutic target combating rapamycin-induced dyslipidemia after LT.

Reduced gonadotroph stimulation by ethanolamine plasmalogens in old bovine brains

Ethanolamine plasmalogens (EPls), unique alkenylacyl-glycerophospholipids, are the only known ligands of G-protein-coupled receptor 61—a novel receptor co-localised with gonadotropin-releasing hormone receptors on anterior pituitary gonadotrophs. Brain EPl decreases with age. Commercial EPl—extracted from the cattle brain (unidentified age)—can independently stimulate FSH secretion from gonadotrophs. We hypothesised that there exists an age-related difference in the quality, quantity, and ability of bovine brain EPls to stimulate bovine gonadotrophs. We compared the brains of young (about 26 month old heifers) and old (about 90 month old cows) Japanese Black bovines, including EPls obtained from both groups. Additionally, mRNA expressions of the EPl biosynthesis enzymes, glyceronephosphate O-acyltransferase, alkylglycerone phosphate synthase, and fatty acyl-CoA reductase 1 (FAR1) were evaluated in young and old hypothalami. The old-brain EPl did not stimulate FSH secretion from gonadotrophs, unlike the young-brain EPl. Molecular species of EPl were compared using two-dimensional liquid chromatography-mass spectrometry. We identified 20 EPl molecular species of which three and three exhibited lower (P < 0.05) and higher (P < 0.05) ratios, respectively, in old compared to young brains. In addition, quantitative reverse transcription-polymerase chain reaction detected higher FAR1 levels in the POA, but not in the ARC&ME tissues, of old cows than that of fertile young heifers. Therefore, old-brain EPl may be associated with age-related infertility.

Effect of alkylglycerone phosphate synthase on the expression levels of lncRNAs in glioma cells and its functional prediction.

Alkylglycerone phosphate synthase (AGPS) is a key enzyme for ether ester synthesis and acts as an oncogene in malignant tumors. The present study aimed to investigate the effect of AGPS silencing on the expression levels of long non-coding RNAs (lncRNAs) and the co-expression with mRNAs in glioma U251 cells using microarray analysis. Furthermore, the underlying biological functions of crucial lncRNAs identified were investigated. It was discovered that in vitro U251 cell proliferation was suppressed following the genetic silencing of AGPS. Differentially expressed lncRNAs and mRNAs in U251 cells were sequenced following AGPS silencing. The results from the Gene Ontology analysis identified that the co-expressed mRNAs were mainly involved in biological processes, such as ‘cellular response to hypoxia’, ‘extracellular matrix organization’ and ‘PERK-mediated unfolded protein response’. In addition, Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis revealed that the co-expressed mRNAs were the most enriched in the ‘AGE/RAGE signaling pathway in diabetic conditions’. Additionally, the PI3K/Akt and epidermal growth factor receptor signaling pathways serve important roles in tumor processes, for example carcinogenesis and angiogenesis. Furthermore, it was identified that the lncRNA AK093732 served a vital role in the regulatory network and the core pathway in this network regulated by this lncRNA was discovered to be the ‘Cytokine-cytokine receptor interaction’. In conclusion, the findings of the present study suggested that AGPS may affect cell proliferation and the degree of malignancy. In addition, the identified lncRNAs and their co-expressed mRNAs screened using microarrays may have significant biological effects in the occurrence, development and metastasis of glioma, and thus may be novel markers of glioma.

Role of the alkylglycerone phosphate synthase in isoproterenol-induced cardiac hypertrophy

Objective To research the effect of alkylation of glycerol phosphate synthase(AGPS) in isoproterenol (ISO) induced rat cardiac hypertrophy. Methods The pathological cardiac hypertrophy rat model was constructed by ISO intraperitoneal injection. Twelve healthy Sprague-Dawley rats (120~150 g) were divided into ISO group and control group randomly. In the ISO group, rats were injected with ISO (3 mg/kg) per day for two consecutive weeks. In the control group, rats were injected with normal saline (3 mg/kg) per day for two consecutive weeks. Changes of left ventricular diastolic diameter, left ventricular posterior wall thickness, left ventricular ejection fraction, left ventricular short-axis shortening rate and left ventricular mass were detected by echocardiography. The cross-sectional area of myocardial cells in rats was measured by hematoxylin-eosin staining. The expression of hypertrophic factors [atrial natriuretic peptide (ANP), myosin light chain-2V (MLC-2V), α-myosin heavy chain (α-MHC)] and AGPS were detected by Western Blot and real-time quantitative PCR (qPCR). Results The results of echocardiography showed that the cardiac hypertrophy rat model was successfully constructed. The results of hematoxylin-eosin staining showed that the myocardial cross-sectional area in the ISO group was significantly larger than that of the control group. The Western Blot and qPCR results indicated that the relative expression of protein and mRNA of hypertrophic factor and AGPS in the ISO group were both up-regulated comparing with that of the control group, and the differences were statistical significance (all P<0.05). Conclusions The rat model of pathological cardiac hypertrophy with up-regulated AGPS expression was successfully constructed providing a theoretical basis for further study on the role of AGPS in pathogenesis of pathological cardiac hypertrophy. Key words: Cardiomyopathy, hypertrophic; Isoproterenol; Alkylglycerone phosphate synthase

Development of alkyl glycerone phosphate synthase inhibitors: Structure-activity relationship and effects on ether lipids and epithelial-mesenchymal transition in cancer cells

In aggressive tumors, alkylglyceronephosphate synthase (AGPS) controls cellular ether phospholipid utilization and metabolism to promote cancer cell proliferation and motility. SAR studies on the first-in-class AGPS inhibitor 1, discovered by our group, led to the 2,6-difluoro analog 2i which showed higher binding affinity than 1in vitro. In 231MFP cancer cells, 2i reduced ether lipids levels and cell migration rate. When tested in PC-3 and MDA-MB-231 cancer cells, 2i specifically impaired epithelial to mesenchymal transition (EMT) by modulating E-cadherin, Snail and MMP2 expression levels. Moreover, the combination of siRNAs against AGPS and 2i provided no additive effect, confirming that the modulation of 2i on EMT specifically relies on AGPS inhibition. Finally, this compound also affected cancer cell proliferation especially in MDA-MB-231 cells expressing higher AGPS level, whereas it provided negligible effects on MeT5A, a non-tumorigenic cell line, thus showing cancer specificity.

PUFA-Plasmalogens Attenuate the LPS-Induced Nitric Oxide Production by Inhibiting the NF-kB, p38 MAPK and JNK Pathways in Microglial Cells

The special lipids plasmalogens (Pls) were reported to be reduced in the neurodegenerative brains such as Alzheimer’s disease where a marked increase of glial activation is often observed. We previously found that a reduction of brain Pls can enhance the glial activation in murine brains. However, the detailed role of Pls in the prevention of glial activation was mostly elusive. Here we report that the Pls, extracted from scallop (sPls), significantly inhibited the inducible form of nitric oxide synthase (NOS2) and the production of NO in LPS (lipopolysaccharide)-activated microglial cells. We also observed that the polyunsaturated docosahexaenoic acid (DHA)-containing Pls but not the monounsaturated oleic acid-containing Pls attenuated the NOS2 induction. In addition, sPls blocked the activation of nuclear factor (NF)-kB and mitogen-activated protein kinases (MAPKs) e.g., JNK and p38 MAPK, thereby attenuated the nuclear translocation of NF-kB subunit, p65, and activator protein-1 (AP-1) proteins (c-Fos and c-Jun). Interestingly, LPS treatments suppressed the expression of Pls synthesizing enzymes, glycerone phosphate O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the microglial cells by the p38MAPK and JNK pathways. Furthermore, the knockdown of GNPAT and AGPS genes by sh-RNAs accelerated the LPS-induced activation of p38MAPK and JNK, resulting in the increased production of NO. These findings suggested that a decrease of brain Pls can activate the NF-kB, p38MAPK and JNK pathways to induce a prolonged microglial activation which may downplay the neuroprotective events in the brains of neurodegenerative diseases.

ADME/toxicity prediction and antitumor activity of novel nitrogenous heterocyclic compounds designed by computer targeting of alkylglycerone phosphate synthase.

Alkylglycerone phosphate synthase (AGPS) is an oncogene and can be considered as an antitumor drug target. The aim of the present study was to design novel nitrogenous heterocyclic compound improving targetability by computer-aided drug design technology targeting AGPS. A total of 12 nitrogenous heterocyclic compounds were designed and predicted the absorption, distribution, metabolism and excretion parameters/toxicity. Their activity in terms of proliferation inhibition, cell cycle arrest and apoptosis induction was then measured using an MTS assay and a high-content screening system in U251 cells. The results showed that anti-glioma activity was present in compounds N4, N5, N6, N7, N8 and N12, which was in accordance with the computer prediction. Therefore, these compounds may be suitable for the development of a novel glioma therapeutic drug.

Computer-aided drug design and inhibitive effect of a novel nitrogenous heterocyclic compound and its mechanism on glioma U251 cells and breast cancer MCF-7 cells.

BackgroundGlioma and breast cancer are severe malignant cancerous tumors that highlight the importance of developing new anti-cancer drugs. The aim of this study was to explore the effects of a novel nitrogenous heterocyclic compound on glioma and breast cancer cells and to determine its mechanism of action.MethodsWe designed and synthesized a novel nitrogenous heterocyclic compound, 3-(4-amino-1H-benzo[d]imidazole-2-carboxamido)-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5] tetrazine-8-carboxamide, based on alkylglycerone phosphate synthase (AGPS) using computer-aided drug design (CADD), and we measured its effect on the proliferation, invasion, cell cycle and apoptosis of U251 glioma and MCF-7 breast cancer cells. In addition, the compound’s effect on the expression of tumor-related mRNA, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) was explored.ResultsIt was found that the nitrogenous heterocyclic compound could induce cell cycle arrest at the G2/M phase of U251/MCF-7 cells and activate apoptosis. Real-time PCR showed that the expression levels of tumor-related mRNA, circRNAs and lncRNAs were impacted.ConclusionWe concluded that the nitrogenous heterocyclic compound inhibits the proliferation and invasion of U251 glioma and MCF-7 breast cancer cells through the induction of apoptosis and cell cycle arrest by regulating tumor-related genes.

Effects of Different Nitrogen Application Rates on Starch Accumulation, Starch Synthase Gene Expression and Enzyme Activity in Two Distinctive Potato Cultivars

Nitrogen (N) is the most important nutrient for potato growth. N fertilizer has an important effect on the tuber yield and starch content in potatoes. In this study, taking the high-starch cultivar Kexin 22 and the low-starch cultivar Kexin 19 as experimental materials, three N fertilizer application rates—0, 150 and 300 kg/ha—were used to investigate the effects of different N application rates on starch accumulation and the expression of starch synthase genes in potato tubers with different starch contents. In the cultivar Kexin 22, the accumulations of amylose, amylopectin and total starch showed a ranking of N150 > N300 > N0 for the entire growth period. The cultivar Kexin 19 showed an accumulation pattern of N0 > N150 > N300 in the early growth period, N150 > N300 > N0 in the middle growth period and N300 > N150 > N0 in the late growth period. Compared with those in Kexin 19, the expressions of the glucose-1-phosphate adenyltransferase (AGPP-L), granule-bound starch synthase (GBSSI), starch-branching enzyme I (SBEI) and soluble starch synthase III (SSIII) genes in Kexin 22 were upregulated, whereas no obvious difference existed in the expression of the alkylglycerone phosphate synthase (AGPP-S) and soluble starch synthase II (SSII) genes between the two cultivars. In Kexin 22, the different N application rates had a significant effect on the peak expression levels of AGPP-L, GBSSI, SBEI and SSIII but had a small effect on the peak expression time for these genes. Among these genes, most showed a ranking of N150 > N300 > N0 in the early and middle growth periods, and all showed a ranking of N300 > N150 > N0 in the late growth period; most showed a peak expression time on the 65th day after emergence (DAE 65). In Kexin 19, the different N application rates had a significant effect on the peak expression levels and peak expression times of the AGPP-L, GBSSI, SBEI and SSIII genes. Among these genes, all showed a ranking of N0 > N150 > N300 in the early growth period, whereas most showed a ranking of N150 > N300 > N0 in the middle growth period, and all showed a ranking of N300 > N150 > N0 in the late growth period. In Kexin 19, the peak gene expression was shifted to an earlier date under the low N levels, and it was delayed under the high N levels. The effects of the N application rate on the activities of starch synthases AGPP, GBSS, SSS and SBE showed largely the same trends as those in the expression levels of the related genes. Therefore, to obtain a high harvest of starch yield, different N application rates should be recommended for different cultivars.

Tudor-staphylococcal nuclease regulates the expression and biological function of alkylglycerone phosphate synthase via nuclear factor-κB and microRNA-127 in human glioma U87MG cells.

Glioma is one of the malignant tumor types detrimental to human health; therefore, it is important to find novel targets and therapeutics for this tumor. The downregulated expression of Tudor-staphylococcal nuclease (SN) and alkylglycerone phosphate synthase (AGPS) can decrease cancer malignancy, and the overexpression of them can the increase viability and migration potential of various tumor cell types; however, the role of AGPS in the proliferation and migration of glioma, and the association of Tudor-SN and AGPS in human glioma is not clear. In the present study, it was determined that AGPS silencing suppressed the proliferation and migration potential of glioma U87MG cells, and suppressed the expression of the circular RNAs circ-ubiquitin-associated protein 2, circ-zinc finger protein 292 and circ-homeodomain-interacting protein kinase 3, and the long non-coding RNAs H19 imprinted maternally expressed transcript (non-protein coding), colon cancer-associated transcript 1 (non-protein coding) and hepatocellular carcinoma upregulated long non-coding RNA. Furthermore, Tudor-SN silencing suppressed the expression of AGPS; however, nuclear factor (NF)-κB and microRNA (miR)-127 retrieval experiments partially reduced the expression of AGPS. Additionally, it was determined that Tudor-SN silencing suppressed the activity of the mechanistic target of rapamycin (mTOR) signaling pathway, and NF-κB and miR-127 retrieval experiments partially reduced the activity of mTOR. Therefore, it was considered that NF-κB and miR-127 may be the mediators of Tudor-SN-regulated AGPS via the mTOR signaling pathway. These results improve on our knowledge of the mechanisms underlying Tudor-SN and AGPS in human glioma.

Effect of alkylglycerone phosphate synthase on the expression profile of circRNAs in the human thyroid cancer cell line FRO.

Thyroid cancer is a common primary tumor in China. Therefore, it is important to investigate the underlying molecular mechanism of thyroid cancer in order to achieve effective individualized treatments. In our previous study, a positive correlation between the expression of alkylglycerone phosphate synthase (AGPS) and the malignant phenotype of thyroid cancer cell lines was identified. The inactivation of AGPS was able to decrease the malignancy of cancer, and inhibit tumor growth and invasion. However, the function of AGPS on thyroid cancer was unclear. In the present study, it was revealed that AGPS was able to regulate the expression of circular RNAs (circRNAs), which may be the mechanism of its anticancer activity. Therefore, the effects of AGPS silencing and knockout on circRNA expression in the thyroid cancer cell line FRO were investigated using circRNAs microarray, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed in order to investigate the underlying molecular mechanism of AGPS for the regulation of thyroid cancer through circRNAs.