scholarly journals Down-regulation of the Genome Uncoupled 4 Retards Starch Biosynthesis in Rice

2020 ◽  
Author(s):  
Ruiqing Li ◽  
Meng Jiang ◽  
Huali Zhang
Keyword(s):  
Target Genes ◽  
Starch Synthesis ◽  
Underlying Mechanism ◽  
Starch Biosynthesis ◽  
Down Regulation ◽  
Dynamic Activity ◽  
High Photosynthetic Capacity ◽  
Storage Carbohydrate ◽  
Physical Functions ◽  
Abnormal Performance

Abstract BackgroundStarch is the major storage carbohydrate in rice, with essential physical functions for plant growth. The starch biosynthesis in rice employs the cooperation of nucleus and plastid, which requires regulation of the signals from nucleus to plastid. However, the plastid-to-nucleus retrograde signals for starch biosynthesis is partly mediated by tetrapyrrole intermediates, i.e., heme, but the underlying mechanism is largely unknown. In previous studies, we revealed that the Genome Uncoupled 4 (OsGUN4) mutation in rice have been revealed to greatly affect tetrapyrrole intermediates but retain a high photosynthetic capacity. ResultsHere, we further found that down-regulation of OsGUN4 promoted to accumulate sucrose but reduce the total starch, attributing to abnormal performance of metabolisms and enzyme activities of starch biosynthesis in leaves of gun4epi. Besides, the exogenous sucrose led to induced starch synthesis but reduced sucrose contents in wild-type, while norflurazon(NF) treatments could eliminate or weaken these inductions. Nevertheless, no changes were detectedbetween check and sucrose treatments in the gun4epi,whereas NF treatment enhanced the trends of increased sucrose but reduced starch,suggesting the roles of OsGUN4 on balance of photosynthesis and starch biosynthesis. Dynamic activity changes of starch biosynthetic enzymes were in accordance with the contents of carbon metabolites. Moreover, RNA sequencing revealed that a great deal DEGs were associated with starch metabolic pathways, with 62 genes being up-regulated and 25 down-regulated in gun4epi. Many genes involved in starch biosynthesis performed down-regulated expression, including the transcription factor of bZIP58 and its target genes of OsBEIIb and OsSSI, which are vital for the formation of amylopectin and starch granules, while displayed up-regulatedexpression of OsSSIIIa and OsGBSSI that promotes the formation of amylose. ConclusionIn conclusion, these findings confirm that OsGUN4 play regulatory roles on biosynthetic genes and enzyme activity in starch biosynthesis.

scholarly journals MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

2017 ◽  
Vol 43 (5) ◽  
pp. 1974-1986 ◽  
Author(s):  
Ximing Wang ◽  
Yanxia Zhang ◽  
Hongshan Wang ◽  
Genshang Zhao ◽  
Xianen Fa
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
H9c2 Cells ◽  
Down Regulation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

scholarly journals Comparative transcriptomics reveals the difference in early endosperm development between maize with different amylose contents

2019 ◽  
Author(s):  
Zhou Jian Qu ◽  
Tu Shu Xu ◽  
Kang Xiao Tian ◽  
Ting Li ◽  
Cheng Li Wang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Genetic Regulation ◽  
Starch Synthesis ◽  
Endosperm Development ◽  
Starch Biosynthesis ◽  
Kernel Weight ◽  
Valuable Insight ◽  
Storage Carbohydrate ◽  
The Difference ◽  
High Amylose

The endosperm is a crucial organ for seeds that plays vital roles in supporting embryo development and determining seed weight and quality. Starch is the predominant storage carbohydrate of the endosperm and accounts for ~70% of the mature maize kernel weight. Nonetheless, because starch biosynthesis is a complex process that is orchestrated by multiple enzymes, the gene regulatory networks of starch biosynthesis, particularly amylose and amylopectin biosynthesis, have not been fully elucidated. Here, through high-throughput RNA sequencing, we developed a temporal transcriptome atlas of the endosperms of high-amylose maize and common maize at 5-, 10-, 15- and 20-day after pollination and found that 21,986 genes are involved in the programming of the high-amylose maize and common maize endosperm. A coexpression analysis identified multiple sequentially expressed gene sets that are closely correlated cellular and metabolic programs and provided valuable insight into the dynamic reprogramming of the transcriptome in common and high-amylose maize. In addition, a number of genes and transcription factors (TFs) were found to be strongly linked to starch synthesis, which might help elucidate the key mechanisms and regulatory networks underlying amylose and amylopectin biosynthesis. This study will aid the understanding of the spatiotemporal patterns and genetic regulation of endosperm development in different types of maize.

scholarly journals Comparative transcriptomics reveals the difference in early endosperm development between maize with different amylose contents

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7528 ◽  
Author(s):  
Jianzhou Qu ◽  
Shutu Xu ◽  
Xiaokang Tian ◽  
Ting Li ◽  
Licheng Wang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Genetic Regulation ◽  
Starch Synthesis ◽  
Endosperm Development ◽  
Starch Biosynthesis ◽  
Kernel Weight ◽  
Valuable Insight ◽  
Storage Carbohydrate ◽  
The Difference ◽  
High Amylose

In seeds, the endosperm is a crucial organ that plays vital roles in supporting embryo development and determining seed weight and quality. Starch is the predominant storage carbohydrate of the endosperm and accounts for ∼70% of the mature maize kernel weight. Nonetheless, because starch biosynthesis is a complex process that is orchestrated by multiple enzymes, the gene regulatory networks of starch biosynthesis, particularly amylose and amylopectin biosynthesis, have not been fully elucidated. Here, through high-throughput RNA sequencing, we developed a temporal transcriptome atlas of the endosperms of high-amylose maize and common maize at 5-, 10-, 15- and 20-day after pollination and found that 21,986 genes are involved in the programming of the high-amylose and common maize endosperm. A coexpression analysis identified multiple sequentially expressed gene sets that are closely correlated with cellular and metabolic programmes and provided valuable insight into the dynamic reprogramming of the transcriptome in common and high-amylose maize. In addition, a number of genes and transcription factors were found to be strongly linked to starch synthesis, which might help elucidate the key mechanisms and regulatory networks underlying amylose and amylopectin biosynthesis. This study will aid the understanding of the spatiotemporal patterns and genetic regulation of endosperm development in different types of maize and provide valuable genetic information for the breeding of starch varieties with different contents.

scholarly journals Comparative transcriptomics reveals the difference in early endosperm development between maize with different amylose contents

2019 ◽  
Author(s):  
Zhou Jian Qu ◽  
Tu Shu Xu ◽  
Kang Xiao Tian ◽  
Ting Li ◽  
Cheng Li Wang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Genetic Regulation ◽  
Starch Synthesis ◽  
Endosperm Development ◽  
Starch Biosynthesis ◽  
Kernel Weight ◽  
Valuable Insight ◽  
Storage Carbohydrate ◽  
The Difference ◽  
High Amylose

The endosperm is a crucial organ for seeds that plays vital roles in supporting embryo development and determining seed weight and quality. Starch is the predominant storage carbohydrate of the endosperm and accounts for ~70% of the mature maize kernel weight. Nonetheless, because starch biosynthesis is a complex process that is orchestrated by multiple enzymes, the gene regulatory networks of starch biosynthesis, particularly amylose and amylopectin biosynthesis, have not been fully elucidated. Here, through high-throughput RNA sequencing, we developed a temporal transcriptome atlas of the endosperms of high-amylose maize and common maize at 5-, 10-, 15- and 20-day after pollination and found that 21,986 genes are involved in the programming of the high-amylose maize and common maize endosperm. A coexpression analysis identified multiple sequentially expressed gene sets that are closely correlated cellular and metabolic programs and provided valuable insight into the dynamic reprogramming of the transcriptome in common and high-amylose maize. In addition, a number of genes and transcription factors (TFs) were found to be strongly linked to starch synthesis, which might help elucidate the key mechanisms and regulatory networks underlying amylose and amylopectin biosynthesis. This study will aid the understanding of the spatiotemporal patterns and genetic regulation of endosperm development in different types of maize.

scholarly journals Interleukin-10-mediated heme oxygenase 1-induced underlying mechanism in inflammatory down-regulation by norfloxacin in cirrhosis

Hepatology ◽  
2011 ◽  
Vol 53 (3) ◽  
pp. 935-944 ◽  
Author(s):  
Isabel Gómez-Hurtado ◽  
Pedro Zapater ◽  
Pablo Bellot ◽  
Sonia Pascual ◽  
Miguel Pérez-Mateo ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Heme Oxygenase 1 ◽  
Down Regulation

Morin Exerts Anti-Diabetic Effects in Human HepG2 Cells Via Down-Regulation of miR-29a

2018 ◽  
Vol 127 (09) ◽  
pp. 615-622 ◽  
Author(s):  
Toktam Razavi ◽  
Shideh Montasser Kouhsari ◽  
Khalil Abnous
Keyword(s):  
Insulin Signaling ◽  
High Glucose ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Expression Level ◽  
Inhibitory Effects ◽  
Down Regulation ◽  
Insulin Mimetic ◽  
Important Regulator ◽  
First Time

Abstract Diabetes mellitus is a complex metabolic disease around the world that is characterized by hyperglycemia resulting from impaired insulin secretion, insulin action, or both. MicroRNA-29a is an important regulator of insulin signaling and gluconeogenesis pathways through IRS2, PI3K and PEPCK expressions which up regulates in Diabetes. Morin is a substantial bioflavonoid which has insulin mimetic effect, and interacting with nucleic acids and proteins. In this study HepG2 cells, were exposed to high glucose to induce diabetic condition. We have determined whether high glucose stimulation might promotes miR-29a expression level in HepG2 cells and subsequently evaluated the Morin treatment effects on this state. In HepG2 cells, high glucose increases miR-29a expression level and decreases its target genes, IRS2 and PI3K expression, and increases associated downstream gene in gluconeogenic pathway, PEPCK. Morin treatment down regulates miR-29a expression level and improves insulin signaling and glucose metabolism. To confirm the inhibitory effects of Morin on miR-29a, we have transfected cells with mimic and inhibitor-miR-29a. This study for the first time identifies that Morin improves diabetic condition through down regulation of the miR-29a level, and suggest that this new inhibitor of miR-29a may be a useful biomedicine to treat diabetes.

scholarly journals Alterations of Growth and Focal Adhesion Molecules in Human Breast Cancer Cells Exposed to the Random Positioning Machine

2021 ◽  
Vol 9 ◽  
Author(s):  
Jayashree Sahana ◽  
Thomas J. Corydon ◽  
Markus Wehland ◽  
Marcus Krüger ◽  
Sascha Kopp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Target Genes ◽  
Interaction Analysis ◽  
Expression Patterns ◽  
Focal Adhesions ◽  
Multicellular Spheroids ◽  
Down Regulation ◽  
Random Positioning Machine ◽  
Mcf 7

In this study, we evaluated changes in focal adhesions (FAs) in two types of breast cancer cell (BCC) lines (differentiated MCF-7 and the triple-negative MDA-MB-231 cell line) exposed to simulated microgravity (s-μg) created by a random positioning machine (RPM) for 24 h. After exposure, the BCC changed their growth behavior and exhibited two phenotypes in RPM samples: one portion of the cells grew as a normal two-dimensional monolayer [adherent (AD) BCC], while the other portion formed three-dimensional (3D) multicellular spheroids (MCS). After 1 h and 30 min (MDA-MB-231) and 1 h 40 min (MCF-7), the MCS adhered completely to the slide flask bottom. After 2 h, MDA-MB-231 MCS cells started to migrate, and after 6 h, a large number of the cells had left the MCS and continued to grow in a scattered pattern, whereas MCF-7 cells were growing as a confluent monolayer after 6 h and 24 h. We investigated the genes associated with the cytoskeleton, the extracellular matrix and FAs. ACTB, TUBB, FN1, FAK1, and PXN gene expression patterns were not significantly changed in MDA-MB-231 cells, but we observed a down-regulation of LAMA3, ITGB1 mRNAs in AD cells and of ITGB1, TLN1 and VCL mRNAs in MDA-MB-231 MCS. RPM-exposed MCF-7 cells revealed a down-regulation in the gene expression of FAK1, PXN, TLN1, VCL and CDH1 in AD cells and PXN, TLN and CDH1 in MCS. An interaction analysis of the examined genes involved in 3D growth and adhesion indicated a central role of fibronectin, vinculin, and E-cadherin. Live cell imaging of eGFP-vinculin in MCF-7 cells confirmed these findings. β-catenin-transfected MCF-7 cells revealed a nuclear expression in 1g and RPM-AD cells. The target genes BCL9, MYC and JUN of the Wnt/β-catenin signaling pathway were differentially expressed in RPM-exposed MCF-7 cells. These findings suggest that vinculin and β-catenin are key mediators of BCC to form MCS during 24 h of RPM-exposure.

scholarly journals Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response

2018 ◽  
Vol 116 (3) ◽  
pp. 1027-1032 ◽  
Author(s):  
Donglim Esther Park ◽  
Jingwei Cheng ◽  
Christian Berrios ◽  
Joan Montero ◽  
Marta Cortés-Cros ◽  
...  
Keyword(s):  
Target Genes ◽  
Underlying Mechanism ◽  
T Antigen ◽  
Sequencing Analysis ◽  
Merkel Cell ◽  
Wild Type ◽  
Synergistic Activation ◽  
P53 Response ◽  
P53 Activation ◽  
Small T Antigen

Merkel cell polyomavirus (MCV) contributes to approximately 80% of all Merkel cell carcinomas (MCCs), a highly aggressive neuroendocrine carcinoma of the skin. MCV-positive MCC expresses small T antigen (ST) and a truncated form of large T antigen (LT) and usually contains wild-type p53 (TP53) and RB (RB1). In contrast, virus-negative MCC contains inactivating mutations in TP53 and RB1. While the MCV-truncated LT can bind and inhibit RB, it does not bind p53. We report here that MCV LT binds to RB, leading to increased levels of ARF, an inhibitor of MDM2, and activation of p53. However, coexpression of ST reduced p53 activation. MCV ST recruits the MYC homologue MYCL (L-Myc) to the EP400 chromatin remodeler complex and transactivates specific target genes. We observed that depletion of EP400 in MCV-positive MCC cell lines led to increased p53 target gene expression. We suspected that the MCV ST–MYCL–EP400 complex could functionally inactivate p53, but the underlying mechanism was not known. Integrated ChIP and RNA-sequencing analysis following EP400 depletion identified MDM2 as well as CK1α, an activator of MDM4, as target genes of the ST–MYCL–EP400 complex. In addition, MCV-positive MCC cells expressed high levels of MDM4. Combining MDM2 inhibitors with lenalidomide targeting CK1α or an MDM4 inhibitor caused synergistic activation of p53, leading to an apoptotic response in MCV-positive MCC cells and MCC-derived xenografts in mice. These results support dual targeting of MDM2 and MDM4 in virus-positive MCC and other p53 wild-type tumors.

scholarly journals High-density lipoprotein remodelled in hypercholesterolaemic blood induce epigenetically driven down-regulation of endothelial HIF-1α expression in a preclinical animal model

2019 ◽  
Vol 116 (7) ◽  
pp. 1288-1299 ◽  
Author(s):  
Soumaya Ben-Aicha ◽  
Rafael Escate ◽  
Laura Casaní ◽  
Teresa Padró ◽  
Esther Peña ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Down Regulation ◽  
Cholesterol Levels ◽  
In Vivo Effects ◽  
Mirna Content

Abstract Aims High-density lipoproteins (HDLs) are circulating micelles that transport proteins, lipids, and miRNAs. HDL-transported miRNAs (HDL-miRNAs) have lately received attention but their effects on vascular cells are not fully understood. Additionally, whether cardiovascular risk factors affect HDL-miRNAs levels and miRNA transfer to recipient cells remains equally poorly known. Here, we have investigated the changes induced by hypercholesterolaemia on HDL-miRNA levels and its effect on recipient endothelial cells (ECs). Methods and results Pigs were kept on a high-fat diet (HC; n = 10) or a normocholesterolaemic chow (NC; n = 10) for 10 days reaching cholesterol levels of 321.0 (229.7–378.5) mg/dL and 74.0 (62.5–80.2) mg/dL, respectively. HDL particles were isolated, purified, and quantified. HDL-miRNA profiling (n = 149 miRNAs) of HC- and NC-HDLs was performed by multipanel qPCR. Cell cultures of porcine aortic ECs were used to determine whether HDL-miRNAs were delivered to ECs. Potential target genes modulated by miRNAs were identified by bioinformatics and candidate miRNAs were validated by molecular analysis. In vivo effects in the coronary arteries of normocholesterolaemic swine administered HC- or NC-HDLs were analysed. Among the HDL-miRNAs, four were found in different amounts in HC- and NC-HDL (P < 0.05). miR-126-5p and -3p and miR-30b-5p (2.7×, 1.7×, and 1.3×, respectively) were found in higher levels and miR-103a-3p and miR-let-7g-5p (−1.6×, −1.4×, respectively) in lower levels in HC-HDL. miR-126-5p and -3p were transferred from HC-HDL to EC (2.5×; P < 0.05), but not from NC-HDL, by a SRB1-mediated mechanism. Bioinformatics revealed that HIF1α was the miR-126 target gene with the highest predictive value, which was accordingly found to be markedly reduced in HC-HDL-treated ECs and in miR126 mimic transfected ECs. In vivo validation confirmed that HIF1α was diminished in the coronary endothelial layer of NC pigs administered HC-HDL vs. those administered NC-HDL (P < 0.05). Conclusion Hypercholesterolaemia induces changes in the miRNA content of HDL enhancing miR126 and its delivery to ECs with the consequent down-regulation of its target gene HIF1α.

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