Network Analysis Reveals Dysregulated Functional Patterns in Type II Diabetic Skin

2021 ◽  
Author(s):  
Chunan Liu ◽  
Sudha Ram ◽  
Bonnie L. Hurwitz
Keyword(s):  
Network Analysis ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Type Ii ◽  
Skin Disorders ◽  
Long Term Effects ◽  
High Blood Glucose ◽  
Keratinocyte Proliferation ◽  
And Migration

Abstract Skin disorders are one of the most common complications of type II diabetes (T2DM). Long-term effects of high blood glucose leave individuals with T2DM more susceptible to cutaneous diseases, but its underlying molecular mechanisms are unclear. Network-based methods consider the complex interactions between genes which can complement the analysis of single genes in previous research. Here, we use network analysis and topological properties to systematically investigate dysregulated gene co-expression patterns in type II diabetic skin with skin samples from the Genotype-Tissue Expression database. Our final network consisted of 8,812 genes from 73 subjects with T2DM and 147 non-T2DM subjects matched for age, sex, and race. Two gene modules significantly related to T2DM were functionally enriched in the pathway lipid metabolism, activated by PPARA and SREBF (SREBP). Transcription factors KLF10, KLF4, SP1, and microRNA-21 were predicted to be important regulators of gene expression in these modules. Intramodular analysis and betweenness centrality identified NCOA6 as the hub gene while KHSRP and SIN3B are key coordinators that influence molecular activities differently between T2DM and non-T2DM populations. We built a TF-miRNA-mRNA regulatory network to reveal the novel mechanism (miR-21-PPARA-NCOA6) of dysregulated keratinocyte proliferation, differentiation, and migration in diabetic skin, which may provide new insights into the susceptibility of skin disorders in T2DM patients. Hub genes and key coordinators may serve as therapeutic targets to improve diabetic skincare.

scholarly journals Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans

2020 ◽  
Vol 117 (6) ◽  
pp. 2968-2977
Author(s):  
Zhiyu Liu ◽  
Herong Shi ◽  
Anthony K. Nzessi ◽  
Anne Norris ◽  
Barth D. Grant ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Surface ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Expression Patterns ◽  
Bmp Signaling ◽  
Type I ◽  
Type Ii ◽  
Bmp Receptors

Tetraspanins are a unique family of 4-pass transmembrane proteins that play important roles in a variety of cell biological processes. We have previously shown that 2 paralogous tetraspanins in Caenorhabditis elegans, TSP-12 and TSP-14, function redundantly to promote bone morphogenetic protein (BMP) signaling. The underlying molecular mechanisms, however, are not fully understood. In this study, we examined the expression and subcellular localization patterns of endogenously tagged TSP-12 and TSP-14 proteins. We found that TSP-12 and TSP-14 share overlapping expression patterns in multiple cell types, and that both proteins are localized on the cell surface and in various types of endosomes, including early, late, and recycling endosomes. Animals lacking both TSP-12 and TSP-14 exhibit reduced cell-surface levels of the BMP type II receptor DAF-4/BMPRII, along with impaired endosome morphology and mislocalization of DAF-4/BMPRII to late endosomes and lysosomes. These findings indicate that TSP-12 and TSP-14 are required for the recycling of DAF-4/BMPRII. Together with previous findings that the type I receptor SMA-6 is recycled via the retromer complex, our work demonstrates the involvement of distinct recycling pathways for the type I and type II BMP receptors and highlights the importance of tetraspanin-mediated intracellular trafficking in the regulation of BMP signaling in vivo. As TSP-12 and TSP-14 are conserved in mammals, our findings suggest that the mammalian TSP-12 and TSP-14 homologs may also function in regulating transmembrane protein recycling and BMP signaling.

scholarly journals OsMGT1 Confers Resistance to Magnesium Deficiency By Enhancing the Import of Mg in Rice

2019 ◽  
Vol 20 (1) ◽  
pp. 207 ◽  
Author(s):  
Ludan Zhang ◽  
Yuyang Peng ◽  
Jian Li ◽  
Xinyue Tian ◽  
Zhichang Chen
Keyword(s):  
Plant Growth ◽  
Molecular Mechanisms ◽  
Magnesium Deficiency ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Mesophyll Cells ◽  
Mg Deficiency ◽  
Biochemical Processes ◽  
Essential Nutrient ◽  
Mg Content

Magnesium (Mg) is an essential nutrient element for plant growth and plays an important role in numerous physiological and biochemical processes. Mg deficiency inhibits plant growth and has become a growing problem for crop productions in agriculture. However, the molecular mechanisms for the resistance to Mg deficiency in plants were not well understood. In this study, we identified a Mg transporter gene OsMGT1 that confers resistance to Mg deficiency in rice (Oryza sativa). The expression of OsMGT1 was highly induced by Mg deficiency in shoots. Investigation of tissue expression patterns revealed that OsMGT1 was mainly expressed in the phloem region; however, Mg deficiency remarkably enhanced its expression in xylem parenchyma and mesophyll cells in shoots. Knockout of OsMGT1 resulted in a significant reduction in Mg content and biomass when grown at Mg-limited conditions. Furthermore, the sensitivity to low-Mg in mutants was intensified by excessive calcium supply. In addition, overexpression of OsMGT1 increased Mg content and biomass under low-Mg supply. In conclusion, our results indicate that OsMGT1 plays an important role in rice Mg import and is required for the resistance to Mg deficiency, which can be utilized for molecular breeding of low-Mg tolerant plants.

scholarly journals Dynamic Changes of Ascorbic Acid Occurring During Fruit Development and Ripening of Actinida Latifolia and Their Associated Molecular Mechanisms Deciphered by Weighted Gene Co-Expression Network Analysis

2020 ◽  
Author(s):  
Hui Xia ◽  
Honghong Deng ◽  
Rongping Hu ◽  
Lijin Lin ◽  
Jin Wang ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Network Analysis ◽  
Fruit Development ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Network Module ◽  
Dynamic Changes ◽  
Fruit Development And Ripening ◽  
Expansion Stage ◽  
Highly Correlated

Abstract Background: Actinidia latifolia is an exceptional source with extremely high ascorbic acid (AsA) content. However, its transcriptome atlas is lacking and how AsA accumulates during fruit development and ripening of this special kiwifruit and its associated molecular mechanisms are still poorly understood.Results: Herein, the dynamic changes of AsA content of six stages of A. latifolia fruit development and ripening determined by HPLC demonstrated a rapid increasing profile during the initial expansion stage with a peak around 60 days after flowering (1194.21±69.25 mg 100g-1 FW), followed by a progressive, albeit not significant decrease tendency and reached the minimum levels (1028.76±31.19 mg 100g-1 FW) at maturity. A high-quality full-length (FL) transcriptome of A. latifolia was successfully constructed by third-generation sequencing for the first time, comprising 326,926 FL non-chimeric reads, 15,505 coding sequences, 2882 transcription factors, 18,797 simple sequence repeats, 3328 long noncoding RNAs, and 231 alternative splicing events. Illumina RNA-seq in combination with weighted gene co-expression network analysis revealed a network module highly correlated (r=0.5, p=0.03) with AsA content. Gene co-expression in this network module was explained by its roles in protein processing in endoplasmic reticulum (ko04141), glycolysis/gluconeogenesis (ko00010), and carbon metabolism (ko01200). Moreover, the expression patterns of genes involved in AsA biosynthesis and metabolism validated by qRT-PCR exhibited a similar trend with AsA accumulation.Conclusions: Overall, the dynamic changes of AsA content and associated key genes and enriched metabolic pathways were deciphered, which paves the way for genetic improvement that aims for development of kiwifruit with super-high AsA content.

scholarly journals Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders

2022 ◽  
Vol 16 (1) ◽  
Author(s):  
Minh Ho ◽  
Brian Thompson ◽  
Jeffrey Nicholas Fisk ◽  
Daniel W. Nebert ◽  
Elspeth A. Bruford ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Gene Family Evolution ◽  
Type I ◽  
Type Ii ◽  
Specific Expression ◽  
Keratin Gene ◽  
Tissue Specific ◽  
Tissue Specific Expression

AbstractIntermediate filament (IntFil) genes arose during early metazoan evolution, to provide mechanical support for plasma membranes contacting/interacting with other cells and the extracellular matrix. Keratin genes comprise the largest subset of IntFil genes. Whereas the first keratin gene appeared in sponge, and three genes in arthropods, more rapid increases in keratin genes occurred in lungfish and amphibian genomes, concomitant with land animal-sea animal divergence (~ 440 to 410 million years ago). Human, mouse and zebrafish genomes contain 18, 17 and 24 non-keratin IntFil genes, respectively. Human has 27 of 28 type I “acidic” keratin genes clustered at chromosome (Chr) 17q21.2, and all 26 type II “basic” keratin genes clustered at Chr 12q13.13. Mouse has 27 of 28 type I keratin genes clustered on Chr 11, and all 26 type II clustered on Chr 15. Zebrafish has 18 type I keratin genes scattered on five chromosomes, and 3 type II keratin genes on two chromosomes. Types I and II keratin clusters—reflecting evolutionary blooms of keratin genes along one chromosomal segment—are found in all land animal genomes examined, but not fishes; such rapid gene expansions likely reflect sudden requirements for many novel paralogous proteins having divergent functions to enhance species survival following sea-to-land transition. Using data from the Genotype-Tissue Expression (GTEx) project, tissue-specific keratin expression throughout the human body was reconstructed. Clustering of gene expression patterns revealed similarities in tissue-specific expression patterns for previously described “keratin pairs” (i.e., KRT1/KRT10, KRT8/KRT18, KRT5/KRT14, KRT6/KRT16 and KRT6/KRT17 proteins). The ClinVar database currently lists 26 human disease-causing variants within the various domains of keratin proteins.

scholarly journals The Vital Roles of LINC00662 in Human Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuting He ◽  
Yating Xu ◽  
Xiao Yu ◽  
Zongzong Sun ◽  
Wenzhi Guo
Keyword(s):  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Expression Patterns ◽  
Clinicopathological Characteristics ◽  
Protein Coding ◽  
Multiple Systems ◽  
Invasion And Migration ◽  
Cellular Events ◽  
Potential Biomarker ◽  
And Migration

Long non-coding RNAs (lncRNAs) play crucial roles in many human diseases, particularly in tumorigenicity and progression. Although lncRNA research studies are increasing rapidly, our understanding of lncRNA mechanisms is still incomplete. The long intergenic non-protein coding RNA 662 (LINC00662) is a novel lncRNA, and accumulating evidence suggests that it is related to a variety of tumors in multiple systems, including the respiratory, reproductive, nervous, and digestive systems. LINC00662 has been shown to be upregulated in malignant tumors and has been confirmed to promote the development of malignant tumors. LINC00662 has also been reported to facilitate a variety of cellular events, such as tumor-cell proliferation, invasion, and migration, and its expression has been correlated to clinicopathological characteristics in patients with tumors. In terms of mechanisms, LINC00662 regulates gene expression by interacting with both proteins and with RNAs, so it may be a potential biomarker for cancer diagnosis, prognosis, and treatment. This article reviews the expression patterns, biological functions, and underlying molecular mechanisms of LINC00662 in tumors.

scholarly journals Hub microRNAs and genes in the development of atrial fibrillation identified by weighted gene co-expression network analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qiang Qu ◽  
Jin-Yu Sun ◽  
Zhen-Ye Zhang ◽  
Yue Su ◽  
Shan-Shan Li ◽  
...  
Keyword(s):  
Network Analysis ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Interaction Patterns ◽  
Hub Genes ◽  
Key Genes

AbstractCo-expression network may contribute to better understanding molecular interaction patterns underlying cellular processes. To explore microRNAs (miRNAs) expression patterns correlated with AF, we performed weighted gene co-expression network analysis (WGCNA) based on the dataset GSE28954. Thereafter, we predicted target genes using experimentally verified databases (ENOCRI, miRTarBase, and Tarbase), and overlapped genes with differentially expressed genes (DEGs) from GSE79768 were identified as key genes. Integrated analysis of association between hub miRNAs and key genes was conducted to screen hub genes. In general, we identified 3 differentially expressed miRNAs (DEMs) and 320 DEGs, predominantly enriched in inflammation-related functional items. Two significant modules (red and blue) and hub miRNAs (hsa-miR-146b-5p and hsa-miR-378a-5p), which highly correlated with AF-related phenotype, were detected by WGCNA. By overlapping the DEGs and predicted target genes, 38 genes were screened out. Finally, 9 genes (i.e. ATP13A3, BMP2, CXCL1, GABPA, LIF, MAP3K8, NPY1R, S100A12, SLC16A2) located at the core region in the miRNA-gene interaction network were identified as hub genes. In conclusion, our study identified 2 hub miRNAs and 9 hub genes, which may improve the understanding of molecular mechanisms and help to reveal potential therapeutic targets against AF.

Type-II Endoleaks Following Endovascular AAA Repair:Preoperative Predictors and Long-term Effects

2001 ◽  
Vol 8 (5) ◽  
pp. 503-510 ◽  
Author(s):  
Frank R. Arko ◽  
Geoffrey D. Rubin ◽  
Bonnie L. Johnson ◽  
Bradley B. Hill ◽  
Thomas J. Fogarty ◽  
...  
Keyword(s):  
Type Ii ◽  
Long Term Effects

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.

Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Donghuan Zhang ◽  
Rui Feng ◽  
Nan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Chorioallantoic Membrane ◽  
Cell Counting ◽  
Biological Behavior ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
Apoptosis Related Protein ◽  
And Migration

Background: Gastric cancer(GC) is currently one of the major malignancies that threatens human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert anti-tumor effects. However, the function in gastric cancer is incompletely understood. Objective: The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Method: Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the cell counting kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken chorioallantoic membrane (CAM) assays. proliferation-associated protein (Ki67), apoptosis-related protein (Bcl-2), and vascular endothelial growth factor A (VEGF-A) were quantified by Western bloting. Results: The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with in control and either drug alone. Conclusion: The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.

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