Downregulation of Methionine Cycle Genes MAT1A and GNMT Enriches Protein-Associated Translation Process and Worsens Hepatocellular Carcinoma Prognosis

The major biological methyl donor, S-adenosylmethionine (adoMet) synthesis occurs mainly in the liver. Methionine adenosyltransferase 1A (MAT1A) and glycine N-methyltransferase (GNMT) are two key enzymes involved in the functional implications of that variation. We collected 42 RNA-seq data from paired hepatocellular carcinoma (HCC) and its adjacent normal liver tissue from the Cancer Genome Atlas (TCGA). There was no mutation found in MAT1A or GNMT RNA in the 42 HCC patients. The 11,799 genes were annotated in the RNA-Seq data, and their expression levels were used to investigate the phenotypes of low MAT1A and low GNMT by Gene Set Enrichment Analysis (GSEA). The REACTOME_TRANSLATION gene set was enriched and visualized in a heatmap along with corresponding differences in gene expression between low MAT1A versus high MAT1A and low GNMT versus high GNMT. We identified 43 genes of the REACTOME_TRANSLATION gene set that are powerful prognosis factors in HCC. The significantly predicted genes were referred into eukaryotic translation initiation (EIF3B, EIF3K), eukaryotic translation elongation (EEF1D), and ribosomal proteins (RPs). Cell models expressing various MAT1A and GNMT proved that simultaneous restoring the expression of MAT1A and GNMT decreased cell proliferation, invasion, as well as the REACTOME_TRANSLATION gene EEF1D, consistent with a better prognosis in human HCC. We demonstrated new findings that downregulation or defect in MAT1A and GNMT genes can enrich the protein-associated translation process that may account for poor HCC prognosis. This is the first study demonstrated that MAT1A and GNMT, the 2 key enzymes involved in methionine cycle, could attenuate the function of ribosome translation. We propose a potential novel mechanism by which the diminished GNMT and MAT1A expression may confer poor prognosis for HCC.

Approaches to Decrease Hyperglycemia by Targeting Impaired Hepatic Glucose Homeostasis Using Medicinal Plants

Liver plays a pivotal role in maintaining blood glucose levels through complex processes which involve the disposal, storage, and endogenous production of this carbohydrate. Insulin is the hormone responsible for regulating hepatic glucose production and glucose storage as glycogen, thus abnormalities in its function lead to hyperglycemia in obese or diabetic patients because of higher production rates and lower capacity to store glucose. In this context, two different but complementary therapeutic approaches can be highlighted to avoid the hyperglycemia generated by the hepatic insulin resistance: 1) enhancing insulin function by inhibiting the protein tyrosine phosphatase 1B, one of the main enzymes that disrupt the insulin signal, and 2) direct regulation of key enzymes involved in hepatic glucose production and glycogen synthesis/breakdown. It is recognized that medicinal plants are a valuable source of molecules with special properties and a wide range of scaffolds that can improve hepatic glucose metabolism. Some molecules, especially phenolic compounds and terpenoids, exhibit a powerful inhibitory capacity on protein tyrosine phosphatase 1B and decrease the expression or activity of the key enzymes involved in the gluconeogenic pathway, such as phosphoenolpyruvate carboxykinase or glucose 6-phosphatase. This review shed light on the progress made in the past 7 years in medicinal plants capable of improving hepatic glucose homeostasis through the two proposed approaches. We suggest that Coreopsis tinctoria, Lithocarpus polystachyus, and Panax ginseng can be good candidates for developing herbal medicines or phytomedicines that target inhibition of hepatic glucose output as they can modulate the activity of PTP-1B, the expression of gluconeogenic enzymes, and the glycogen content.

Physiological and Biochemical Responses, and Comparative Transcriptome Profiling of Two Angelica sinensis Cultivars Under Enhanced Ultraviolet-B Radiation

In this study, we explored the adaptive mechanism of two varieties of Angelica sinensis exposed to enhanced Ultraviolet-B (UV-B) radiation. The radiation had different effects on the biomass, photosynthetic performance, oxidative damage, antioxidant defense system, and levels of bioactive compounds of Mingui 1 (C1) and Mingui 2 (C2). C2 outperformed C1 under enhanced UV-B radiation, compared to natural light. Using the Illumina RNA-seq, we obtained 6,326 and 2,583 DEGs in C1 and C2, respectively. Under enhanced UV-B radiation, the mRNA levels of genes involved in photosynthesis, antennae protein synthesis, carbon fixation, chlorophyll synthesis, and carotenoid synthesis were decreased in C1 but stable in C2, involving few DEGs. TFs were widely involved in the response of C1 to enhanced UV-B radiation; almost all bHLH and MYB coding genes were downregulated whereas almost all genes encoded WRKY22, WRKY50, WRKY72, NCF, and HSF were upregulated. These results indicate that enhanced UV-B radiation was not conducive to the synthesis of flavonoids, while disease resistance was enhanced. Regarding the ROS scavenging system, upregulated DEGs were mainly found in the AsA-GSH cycle and PrxR/Trx pathways. Remarkably, DEGs that those encoding biosynthetic key enzymes, including ferulic acid (CHS, CHI, DFR, and ANS) and flavonoid (CHS, CHI, DFR, and ANS), most upregulation in C2, leading to increased accumulation of ferulic acid and flavonoids and adversely affecting C1. Genes encoding key enzymes involved in the synthesis of lactone components (ACX, PXG) were mostly up-regulated in C1, increasing the content of lactone components. Our results reveal the DEGs present between C1 and C2 under enhanced UV-B radiation and are consistent with the observed differences in physiological and biochemical indexes. C1 was more sensitive to enhanced UV-B radiation, and C2 was more tolerant to it under moderate enhanced UV-B radiation stress. In addition, the large amount of A. sinensis transcriptome data generated here will serve as a source for finding effective ways to mitigate UV-B enhancement, and also contribute to the well-established lack of genetic information for non-model plant species.

From fruit growth to ripening in plantain: a careful balance between carbohydrate synthesis and breakdown

We investigated the fruit development in two plantain banana cultivars from two weeks after bunch emergence till twelve weeks through high-throughput proteomics, major metabolite quantification and metabolic flux analyses. We give for the first time an insight at early stages of starch synthesis and breakdown. Starch and sugar synthesis and breakdown are processes that take place simultaneously. During the first eight to ten weeks the balance between synthesis and breakdown is clearly in favour of sugar breakdown and a net starch synthesis occurs. During this period, plantain fruit accumulates up to 48% of starch. The initiation of the ripening process is accompanied with a shift in balance towards net starch breakdown. The key enzymes related to this are phosphoglucan water dikinase (PWD), phosphoglucan phosphatase, α-1,6-glucosidase starch debranching enzyme (DBE), alpha glucan phosphorylase (PHS) and 4-alpha glucanotransferase disproportioning enzyme (DPE). The highest correlations with sucrose have been observed for PHS and DPE. There is also a significant correlation between the enzymes involved in ethylene biosynthesis, starch breakdown, pulp softening and ascorbate biosynthesis. The faster ending of maturation and starting of ripening in the Agbagba cultivar are linked to the key enzymes 1-aminocyclopropane-1-carboxylate oxidase and DPE. This knowledge of the mechanisms that regulate starch and sugar metabolisms during maturation and ripening is fundamental to determine the harvest moment, reduce postharvest losses and improve final product quality of breeding programs.