scholarly journals Comparative Transcriptomic and Physiological Analyses of Medicago sativa L. Indicates that Multiple Regulatory Networks Are Activated during Continuous ABA Treatment

2018 ◽  
Vol 20 (1) ◽  
pp. 47 ◽  
Author(s):  
Dong Luo ◽  
Yuguo Wu ◽  
Jie Liu ◽  
Qiang Zhou ◽  
Wenxian Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Abiotic Stress Tolerance ◽  
Pathogen Resistance ◽  
Control Group ◽  
Antioxidative Defense ◽  
Sequencing Platform ◽  
Medicago Sativa L ◽  
Transcript Profiles

Alfalfa is the most extensively cultivated forage legume worldwide. However, the molecular mechanisms underlying alfalfa responses to exogenous abscisic acid (ABA) are still unknown. In this study, the first global transcriptome profiles of alfalfa roots under ABA treatments for 1, 3 and 12 h (three biological replicates for each time point, including the control group) were constructed using a BGISEQ-500 sequencing platform. A total of 50,742 isoforms with a mean length of 2541 bp were generated, and 4944 differentially expressed isoforms (DEIs) were identified after ABA deposition. Metabolic analyses revealed that these DEIs were involved in plant hormone signal transduction, transcriptional regulation, antioxidative defense and pathogen immunity. Notably, several well characterized hormone signaling pathways, for example, the core ABA signaling pathway, was activated, while salicylic acid, jasmonate and ethylene signaling pathways were mainly suppressed by exogenous ABA. Moreover, the physiological work showed that catalase and peroxidase activity and glutathione and proline content were increased after ABA deposition, which is in accordance with the dynamic transcript profiles of the relevant genes in antioxidative defense system. These results indicate that ABA has the potential to improve abiotic stress tolerance, but that it may negatively regulate pathogen resistance in alfalfa.

scholarly journals Multiple Regulatory Networks Are Activated during Cold Stress in Medicago sativa L.

2018 ◽  
Vol 19 (10) ◽  
pp. 3169 ◽  
Author(s):  
Qiang Zhou ◽  
Dong Luo ◽  
Xutian Chai ◽  
Yuguo Wu ◽  
Yanrong Wang ◽  
...  
Keyword(s):  
Cold Stress ◽  
Medicago Sativa ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Sequencing Platform ◽  
Medicago Sativa L ◽  
Perennial Legume

Cultivated alfalfa (Medicago sativa L.) is one of the most important perennial legume forages in the world, and it has considerable potential as a valuable forage crop for livestock. However, the molecular mechanisms underlying alfalfa responses to cold stress are largely unknown. In this study, the transcriptome changes in alfalfa under cold stress at 4 °C for 2, 6, 24, and 48 h (three replicates for each time point) were analyzed using the high-throughput sequencing platform, BGISEQ-500, resulting in the identification of 50,809 annotated unigenes and 5283 differentially expressed genes (DEGs). Metabolic pathway enrichment analysis demonstrated that the DEGs were involved in carbohydrate metabolism, photosynthesis, plant hormone signal transduction, and the biosynthesis of amino acids. Moreover, the physiological changes of glutathione and proline content, catalase, and peroxidase activity were in accordance with dynamic transcript profiles of the relevant genes. Additionally, some transcription factors might play important roles in the alfalfa response to cold stress, as determined by the expression pattern of the related genes during 48 h of cold stress treatment. These findings provide valuable information for identifying and characterizing important components in the cold signaling network in alfalfa and enhancing the understanding of the molecular mechanisms underlying alfalfa responses to cold stress.

scholarly journals Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tarun Karthik Kumar Mamidi ◽  
Jiande Wu ◽  
Chindo Hicks
Keyword(s):  
Signaling Pathways ◽  
Somatic Mutation ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Multiple Gene ◽  
Gene Regulatory ◽  
Aggressive Tumors ◽  
Prostate Cancers ◽  
Mutation Information

Background. A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods. We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results. We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion. The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

scholarly journals Diquat Determines a Deregulation of lncRNA and mRNA Expression in the Liver of Postweaned Piglets

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jin Wang ◽  
Zhi-xin Li ◽  
Dan-dan Yang ◽  
Pei-qi Liu ◽  
Zhi-qiang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Performance ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Reduction Process ◽  
Future Research ◽  
Control Group ◽  
Oxidoreductase Activity ◽  
Go Terms ◽  
Porcine Hepatocytes

Oxidative stress is detrimental to animals and can depress the growth performance and regulate the gene expression of animals. However, it remains unclear how oxidative stress regulates the expression of long noncoding RNAs (lncRNAs) and mRNAs. Therefore, the purpose of this article was to explore the profiles of lncRNAs and mRNAs in the liver of piglets under oxidative stress. Here, we constructed a piglet oxidative stress model induced by diquat and evaluated the effects of oxidative stress on the growth performance and antioxidant enzyme activity of piglets. We also used RNA-Seq to examine the global expression of lncRNAs and mRNAs in piglets under oxidative stress. The targets of lncRNAs and mRNAs were enriched in gene ontology (GO) terms and signaling pathways. The results show that the growth performance and activities of antioxidant enzymes were decreased in piglets under oxidative stress. Moreover, eight lncRNAs (6 upregulated and 2 downregulated) and 30 mRNAs (8 upregulated and 22 downregulated) were differentially expressed in the oxidative stress group of piglets compared to the negative control group. According to biological processes in enriched GO terms, the oxoacid metabolic process, intramolecular oxidoreductase activity, and oxidation-reduction process play important roles in oxidative stress. Pathway analysis showed that the signaling pathways involved in insulin and glucose metabolism had a close relationship with oxidative stress. Furtherin vitroexperiments showed that the expression of the upregulated geneGNMTwas significantly increased in primary porcine hepatocytes after diquat stimulation. In contrast, the level of the downregulated geneGCKwas significantly decreased at 12 h in primary porcine hepatocytes after diquat stimulation. Our results expand our knowledge of the lncRNAs and mRNAs transcribed in the livers of piglets under oxidative stress and provide a basis for future research on the molecular mechanisms mediating oxidative stress and tissue damage.

scholarly journals Interpretation of Fiber Supplementation on Offspring Testicular Development in a Pregnant Sow Model from a Proteomics Perspective

2019 ◽  
Vol 20 (18) ◽  
pp. 4549 ◽  
Author(s):  
Yan Lin ◽  
Lujie Li ◽  
Yang Li ◽  
Ke Wang ◽  
Dongqin Wei ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Renin Angiotensin System ◽  
The Body ◽  
Male Reproduction ◽  
Glutathione Metabolism ◽  
Control Group ◽  
Testicular Development ◽  
Valuable Insight

To study the effects of maternal fiber supplementation during pregnancy on the testicular development of male offspring and its possible mechanisms, 36 sows (Landrace × Yorkshire) were allocated to either a control diet (n = 18) or a fiber diet (the control diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulosic; n = 18) during pregnancy. The body and testes weight of the offspring, 7-day-old piglets, was recorded. Testes were collected for further analyses. Results showed that the testicular organ index and the number of spermatogonia in single seminiferous tubule were higher in piglets from the fiber group than from the control group (p < 0.05). In addition, a significant increase in the concentration of glucose, lactate, and lipids in the testes was found in the fiber group (p < 0.05). Proteomic analysis suggested that there were notable differences in glucolipid transport and metabolism, oxidation, and male reproduction-related proteins expression between the two groups (p < 0.05). Results revealed that the most enriched signaling pathways in the fiber group testes included starch and sucrose metabolism, fatty acid metabolism, glutathione metabolism, and the renin-angiotensin system. mRNA expression analyzes further confirmed the importance of some signaling pathways in maternal fiber nutrition regulating offspring testicular development. Our results shed new light on the underlying molecular mechanisms of maternal fiber nutrition on offspring testicular development and provided a valuable insight for future explorations of the effect of maternal fiber nutrition on man reproduction.

scholarly journals nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks

ExRNA ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
P. Khurana ◽  
A. Gupta ◽  
R. Sugadev ◽  
Y. K. Sharma ◽  
R. Varshney ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Antigen Presentation ◽  
Signaling Pathways ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Mirna Gene ◽  
Protein Stabilization ◽  
Molecular Signature ◽  
Potential Candidate ◽  
Regulatory Circuits

Abstract Background Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. Results and conclusion A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it’s associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth.

scholarly journals Mapping a Circular RNA–microRNA–mRNA-Signaling Regulatory Axis that Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 7864
Author(s):  
Vimalan Rengganaten ◽  
Chiu-Jung Huang ◽  
Ping-Hsing Tsai ◽  
Mong-Lien Wang ◽  
Yi-Ping Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Circular Rna ◽  
Circular Rnas ◽  
Core Network ◽  
Mrna Targets ◽  
Lineage Differentiation

Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA–microRNA (miRNA)–mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA–miRNA–mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.

scholarly journals UTRN inhibits melanoma growth by suppressing p38 and JNK/c-Jun signaling pathways

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sitong Zhou ◽  
Wen Ouyang ◽  
Xi Zhang ◽  
Lexi Liao ◽  
Xiaobing Pi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Cell Counting ◽  
Clinical Samples ◽  
Control Group ◽  
Proliferation Ability ◽  
Melanoma Growth

Abstract Background Utrophin (UTRN), as a tumor suppressor gene, is involved in various cancer progression. The function of UTRN in the melanoma process and the related molecular mechanisms are still unclear. Herein, we studied the function of UTRN in melanoma growth and the relevant molecular mechanisms. Methods Using the GEO database and UCSC Xena project, we compared the expression of UTRN in non-cancerous and melanoma tissues. Immunohistochemistry (IHC) staining, qRT-PCR and Western Blot (WB) were performed to evaluate UTRN expression in clinical samples. A total of 447 cases with UTRN expression data, patient characteristics and survival data were extracted from TCGA database and analyzed. After stable transduction and single cell cloning, the proliferation ability of A375 human melanoma cells was analyzed by Cell Counting Kit‑8 (CCK) and 5‑ethynyl‑2′‑deoxyuridine (EdU) incorporation assays. GSEA was performed to predict the mechanism by which UTRN regulated melanoma growth. Then WB analysis was used to assess the protein expression levels of pathway signaling in overexpression (EXP) melanoma cells. Epac activator 8-pCPT-2′-O-Me-cAMP was then used to evaluate the proliferation ability by activation of p38 and JNK/c-Jun signaling pathways. Results Data from GEO and UCSC Xena project indicated that UTRN expression was decreased in melanoma. Experiment on clinical samples further confirmed our finding. TCGA results showed that a reduced expression of UTRN in 447 melanoma samples was associated with advanced clinical characteristics (T stage, Clark level, ulceration), shorter survival time and poorer prognosis. In addition, up-regulated UTRN expression inhibited melanoma cell proliferation when compared to control group. MAPK signaling pathway was presented in both KEGG and BioCarta databases by using GSEA tool. WB results confirmed the down-regulated expression of p38, JNK1 and c-Jun in EXP group when compared to control group. Epac activator 8-pCPT-2′-O-Me-cAMP treatment could partially rescue proliferation of tumor cells. Conclusion We have demonstrated that reduced UTRN predicted poorer prognosis and UTRN inhibited melanoma growth via p38 and JNK1/c-Jun pathways. Therefore, UTRN could serve as a tumor suppressor and novel prognostic biomarker for melanoma patients.

scholarly journals Multi–Omics Analysis of Key microRNA–mRNA Metabolic Regulatory Networks in Skeletal Muscle of Obese Rabbits

2021 ◽  
Vol 22 (8) ◽  
pp. 4204
Author(s):  
Yanhong Li ◽  
Jie Wang ◽  
Mauricio A. Elzo ◽  
Mingchuan Gan ◽  
Tao Tang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Muscle Metabolism ◽  
Rabbit Skeletal Muscle ◽  
Differentially Expressed ◽  
Control Group ◽  
Small Rna Sequencing ◽  
Non Coding Rna

microRNAs (miRNAs), small non-coding RNA with a length of about 22 nucleotides, are involved in the energy metabolism of skeletal muscle cells. However, their molecular mechanism of metabolism in rabbit skeletal muscle is still unclear. In this study, 16 rabbits, 8 in the control group (CON–G) and 8 in the experimental group (HFD–G), were chosen to construct an obese model induced by a high–fat diet fed from 35 to 70 days of age. Subsequently, 54 differentially expressed miRNAs, 248 differentially expressed mRNAs, and 108 differentially expressed proteins related to the metabolism of skeletal muscle were detected and analyzed with three sequencing techniques (small RNA sequencing, transcriptome sequencing, and tandem mass tab (TMT) protein technology). It was found that 12 miRNAs and 12 core genes (e.g., CRYL1, VDAC3 and APIP) were significantly different in skeletal muscle from rabbits in the two groups. The network analysis showed that seven miRNA-mRNA pairs were involved in metabolism. Importantly, two miRNAs (miR-92a-3p and miR-30a/c/d-5p) regulated three transcription factors (MYBL2, STAT1 and IKZF1) that may be essential for lipid metabolism. These results enhance our understanding of molecular mechanisms associated with rabbit skeletal muscle metabolism and provide a basis for future studies in the metabolic diseases of human obesity.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells

2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Nerve Fibers ◽  
Retinal Ganglion

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

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