The Genomic Impact of Mycoheterotrophy in Orchids

Mycoheterotrophic plants have lost the ability to photosynthesize and obtain essential mineral and organic nutrients from associated soil fungi. Despite involving radical changes in life history traits and ecological requirements, the transition from autotrophy to mycoheterotrophy has occurred independently in many major lineages of land plants, most frequently in Orchidaceae. Yet the molecular mechanisms underlying this shift are still poorly understood. A comparison of the transcriptomes of Epipogium aphyllum and Neottia nidus-avis, two completely mycoheterotrophic orchids, to other autotrophic and mycoheterotrophic orchids showed the unexpected retention of several genes associated with photosynthetic activities. In addition to these selected retentions, the analysis of their expression profiles showed that many orthologs had inverted underground/aboveground expression ratios compared to autotrophic species. Fatty acid and amino acid biosynthesis as well as primary cell wall metabolism were among the pathways most impacted by this expression reprogramming. Our study suggests that the shift in nutritional mode from autotrophy to mycoheterotrophy remodeled the architecture of the plant metabolism but was associated primarily with function losses rather than metabolic innovations.

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The genomic impact of mycoheterotrophy: targeted gene losses but extensive expression reprogramming

10.1101/2020.06.26.173617 ◽

2020 ◽

Author(s):

Jakalski Marcin ◽

Minasiewicz Julita ◽

Caius José ◽

Michał May ◽

Selosse Marc-André ◽

...

Keyword(s):

Life History Traits ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Primary Cell Wall ◽

Cell Wall Metabolism ◽

Ecological Requirements ◽

Nutritional Mode ◽

Mycoheterotrophic Plants ◽

Almost All ◽

Photosynthetic Activities

ABSTRACTMycoheterotrophic plants have lost the ability to photosynthesize and they parasitize their associated fungus to get the mineral and organic nutrients they need. Despite involving radical changes in life history traits and ecological requirements, the transition from autotrophy to mycoheterotrophy occurred independently in almost all major lineages of land plants, but most often in Orchidaceae. Yet the molecular mechanisms underlying this shift are still poorly understood. The comparison of the transcriptomes of Epipogium aphyllum and Neottia nidus-avis, two mycoheterotrophic orchids, to other autotrophic and mycoheterotrophic orchids showed massive molecular function losses restricted to photosynthetic activities. In addition to these targeted losses, the analysis of their expression profiles showed that many orthologs had inverted root/shoot ratios compared to autotrophic species. Fatty acid and amino acid biosynthesis as well as primary cell wall metabolism were among the pathways most impacted by this expression reprogramming. Our study suggests that, while associated with function losses rather than metabolic innovations, the shift in nutritional mode from autotrophy to mycoheterotrophy remodeled the architecture of the plant metabolism.

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Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

Pharmaceuticals ◽

10.3390/ph14010041 ◽

2021 ◽

Vol 14 (1) ◽

pp. 41

Author(s):

Hana Votavova ◽

Zuzana Urbanova ◽

David Kundrat ◽

Michaela Dostalova Merkerova ◽

Martin Vostry ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Blood Cell ◽

Myelodysplastic Syndrome ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Adaptive Immune Response ◽

Gene Expression Profiles ◽

Iron Chelator ◽

Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

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In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

Scientific Reports ◽

10.1038/s41598-021-88698-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kolja Becker ◽

Holger Klein ◽

Eric Simon ◽

Coralie Viollet ◽

Christian Haslinger ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Rna Sequencing ◽

Molecular Mechanisms ◽

Vision Loss ◽

Ganglion Cells ◽

Expression Profiles ◽

Cell Types ◽

Sequencing Data ◽

Disease Stages ◽

Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

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Genome-Wide Mapping of Histone H3 Lysine 4 Trimethylation (H3K4me3) and Its Involvement in Fatty Acid Biosynthesis in Sunflower Developing Seeds

Plants ◽

10.3390/plants10040706 ◽

2021 ◽

Vol 10 (4) ◽

pp. 706

Author(s):

Antonio J. Moreno-Pérez ◽

Raquel Martins-Noguerol ◽

Cristina DeAndrés-Gil ◽

Mónica Venegas-Calerón ◽

Rosario Sánchez ◽

...

Keyword(s):

Fatty Acid ◽

Chromatin Remodeling ◽

Molecular Mechanisms ◽

Acid Metabolism ◽

Fatty Acid Biosynthesis ◽

Acid Synthesis ◽

Sunflower Seeds ◽

Acid Biosynthesis ◽

Functional Regions ◽

Genome Wide

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.

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Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression

Cell Death and Disease ◽

10.1038/s41419-021-03911-5 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Peng Li Zhou ◽

Zhengyang Wu ◽

Wenguang Zhang ◽

Miao Xu ◽

Jianzhuang Ren ◽

...

Keyword(s):

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Epithelial Mesenchymal Transition ◽

Expression Profiles ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Mesenchymal Transition ◽

Dismal Prognosis ◽

Advanced Tumor

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

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SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01933-7 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Qiao Li ◽

Manran Liu ◽

Yan Sun ◽

Ting Jin ◽

Pengpeng Zhu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Histological Grade ◽

Metabolic Adaptation ◽

Mitochondrial Activity ◽

Cell Viability Assay ◽

Ki 67 ◽

The Impact

Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia. Methods RNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O2 and 1% O2). Expressions of Slc6a8, which encodes the creatine transporter protein, were detected in breast cancer cells and tissues by quantitative real-time PCR. Immunohistochemistry was performed to detect SLC6A8 protein abundances in tumor tissues. Clinicopathologic correlation and overall survival were evaluated by chi-square test and Kaplan-Meier analysis, respectively. Cell viability assay and flow cytometry analysis with Annexin V/PI double staining were performed to investigate the impact of SLC6A8-mediated uptake of creatine on viability of hypoxic TNBC cells. TNBC orthotopic mouse model was used to evaluate the effects of creatine in vivo. Results SLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3. Conclusions Our study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.

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Comparative Transcriptomic Analysis of Riptortus pedestris (Hemiptera: Alydidae) to Characterize Wing Formation across All Developmental Stages

Insects ◽

10.3390/insects12030226 ◽

2021 ◽

Vol 12 (3) ◽

pp. 226

Author(s):

Siying Fu ◽

Yujie Duan ◽

Siqi Wang ◽

Yipeng Ren ◽

Wenjun Bu

Keyword(s):

Molecular Mechanisms ◽

Developmental Stages ◽

Average Length ◽

Transcriptome Assembly ◽

Expression Profiles ◽

Economic Losses ◽

Future Research ◽

Economic Damage ◽

Wing Formation ◽

Riptortus Pedestris

Riptortus pedestris (Hemiptera: Alydidae) is a major agricultural pest in East Asia that causes considerable economic losses to the soybean crop each year. However, the molecular mechanisms governing the growth and development of R. pedestris have not been fully elucidated. In this study, the Illumina HiSeq6000 platform was employed to perform de novo transcriptome assembly and determine the gene expression profiles of this species across all developmental stages, including eggs, first-, second-, third-, fourth-, and fifth-instar nymphs, and adults. In this study, a total of 60,058 unigenes were assembled from numerous raw reads, exhibiting an N50 length of 2126 bp and an average length of 1199 bp, and the unigenes were annotated and classified with various databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Gene Ontology (GO). Furthermore, various numbers of differentially expressed genes (DEGs) were calculated through pairwise comparisons of all life stages, and some of these DEGs were associated with immunity, metabolism, and development by GO and KEGG enrichment. In addition, 35,158 simple sequence repeats (SSRs) and 715,604 potential single nucleotide polymorphisms (SNPs) were identified from the seven transcriptome libraries of R. pedestris. Finally, we identified and summarized ten wing formation-related signaling pathways, and the molecular properties and expression levels of five wing development-related genes were analyzed using quantitative real-time PCR for all developmental stages of R. pedestris. Taken together, the results of this study may establish a foundation for future research investigating developmental processes and wing formation in hemimetabolous insects and may provide valuable data for pest control efforts attempting to reduce the economic damage caused by this pest.

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Primary cell wall metabolism: tracking the careers of wall polymers in living plant cells

New Phytologist ◽

10.1111/j.1469-8137.2004.00980.x ◽

2004 ◽

Vol 161 (3) ◽

pp. 641-675 ◽

Cited By ~ 268

Author(s):

Stephen C. Fry

Keyword(s):

Cell Wall ◽

Plant Cells ◽

Primary Cell ◽

Primary Cell Wall ◽

Cell Wall Metabolism ◽

Living Plant

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Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

Reproduction ◽

10.1530/rep-14-0095 ◽

2014 ◽

Vol 148 (1) ◽

pp. 33-41 ◽

Cited By ~ 48

Author(s):

Fulu Dong ◽

Yuan Zhang ◽

Fei Xia ◽

Yi Yang ◽

Sidong Xiong ◽

...

Keyword(s):

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Target Genes ◽

Expression Profiles ◽

Normal Pregnancy ◽

Recurrent Spontaneous Abortion ◽

Future Research ◽

Rna Molecules ◽

Non Coding Rna ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.

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Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Blood ◽

10.1182/blood-2004-01-0103 ◽

2004 ◽

Vol 104 (13) ◽

pp. 4210-4218 ◽

Cited By ~ 104

Author(s):

Guibin Chen ◽

Weihua Zeng ◽

Akira Miyazato ◽

Eric Billings ◽

Jaroslaw P. Maciejewski ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Small Sample ◽

Hematopoietic Progenitor Cell ◽

Molecular Characteristics ◽

Hematopoietic Progenitor ◽

Trisomy 8 ◽

Monosomy 7 ◽

Cd34 Cells

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

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