scholarly journals Systems Genetics Analysis Defines Importance Of TMEM43/LUMA For Cardiac And Metabolic Related Pathways

2021 ◽  
Author(s):  
Qingqing Gu ◽  
Fuyi Xu ◽  
Buyan-Ochir Orgil ◽  
Zaza Khuchua ◽  
Undral Munkhsaikhan ◽  
...  
Keyword(s):  
Gene Networks ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Genetic Regulation ◽  
Reference Population ◽  
Functional Enrichment ◽  
High Density Lipoproteins ◽  
Systems Genetics ◽  
Cellular Functions ◽  
Alcoholic Fatty Liver ◽  
Plasma High Density

Background: Broad cellular functions and diseases including muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC5) and cancer are associated with transmembrane protein43 (TMEM43/LUMA). Objective: The study aimed to investigate biological roles of TMEM43 through genetic regulation, gene pathways and gene networks, candidate interacting genes and up- or down-stream regulators. Methods: Cardiac transcriptomes from 40 strains of recombinant inbred BXD mice and two parental strains representing murine genetic reference population (GRP) was applied for genetic correlation, functional enrichment and co-expression network analysis using systems genetics approach. The results were validated in a newly created knock-in Tmem43-S358L mutation mouse model (Tmem43S358L) that displayed signs of cardiac dysfunction, resembling ARVC5 phenotype seen in humans. Results: We found high Tmem43 levels among BXDs with broad variability in expression. Expression of Tmem43 highly negatively correlated with heart mass and heart rate among BXDs, while levels of Tmem43 highly positively correlated with plasma high density lipoproteins (HDL). Through finding differentially expressed genes (DEGs) between Tmem43S358L mutant and wild type (Tmem43WT) lines, 18 pathways (out of 42 found in BXDs GRP) that are involved in ARVC, Hypertrophic cardiomyopathy, Dilated cardiomyopathy, Non-alcoholic fatty liver disease, Alzheimer disease, Parkinson disease and Huntington disease were verified. We further constructed Tmem43-mediated gene network, in which Ctnna1, Adcy6, Gnas, Ndufs6 and Uqcrc2 were significantly altered in Tmem43S358L mice vs Tmem43WT controls. Conclusions: Our study defined the importance of Tmem43 for cardiac and metabolism related pathways, suggesting that cardiovascular disease-relevant risk factors may also increase risk of metabolic and neurodegenerative diseases via TMEM43-mediated pathways.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

scholarly journals High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad and the Future

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 857
Author(s):  
Josep Julve ◽  
Joan Carles Escolà-Gil
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
High Density ◽  
High Density Lipoproteins ◽  
Atherosclerotic Cardiovascular Disease ◽  
Plasma High Density ◽  
Low Levels

Epidemiological studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]

scholarly journals A 70-kDa apolipoprotein designated ApoJ is a marker for subclasses of human plasma high density lipoproteins.

1990 ◽  
Vol 265 (22) ◽  
pp. 13240-13247 ◽  
Author(s):  
H V de Silva ◽  
W D Stuart ◽  
C R Duvic ◽  
J R Wetterau ◽  
M J Ray ◽  
...  
Keyword(s):  
Human Plasma ◽  
High Density ◽  
High Density Lipoproteins ◽  
Plasma High Density

scholarly journals miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 545 ◽  
Author(s):  
Wei Wu ◽  
Lingxiang Wu ◽  
Mengyan Zhu ◽  
Ziyu Wang ◽  
Min Wu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Target Genes ◽  
Expression Profiles ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Cellular Functions ◽  
Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

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