Chronic alcohol consumption from adolescence-to-adulthood in mice - hypothalamic gene expression changes in the dilated cardiomyopathy signaling pathway

Zou, Hong; Wang, Ke; Gao, Yang; Song, Huaiguang; Xie, Qinglian; Jin, Meilei; Zhao, Guoping; Xiao, Huasheng; Yu, Lei

doi:10.1186/1471-2202-15-61

Cited by 12 publications

(8 citation statements)

References 90 publications

(81 reference statements)

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“…MYB is a nuclear protein and acts as a transcription factor for many cellular pathways in cardiac development ( 35 ). Adenylate cyclase (ADCY1) is involved in cardiac development and cardiomyopathy ( 36 ). HSPB8 is a heat shock protein and is also involved in cardiac development and cardiomyopathy ( 37 ).…”

Section: Resultsmentioning

confidence: 99%

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Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Tian

Niu

Liu

et al. 2021

Front. Cardiovasc. Med.

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Long noncoding RNAs have gained widespread attention in recent years for their crucial role in biological regulation. They have been implicated in a range of developmental processes and diseases including cancer, cardiovascular, and neuronal diseases. However, the role of long noncoding RNAs (lncRNAs) in left ventricular noncompaction (LVNC) has not been explored. In this study, we investigated the expression levels of lncRNAs in the blood of LVNC patients and healthy subjects to identify differentially expressed lncRNA that develop LVNC specific biomarkers and targets for developing therapies using biological pathways. We used Agilent Human lncRNA array that contains both updated lncRNAs and mRNAs probes. We identified 1,568 upregulated and 1,141 downregulated (log fold-change > 2.0) lncRNAs that are differentially expressed between LVNC and the control group. Among them, RP11-1100L3.7 and XLOC_002730 are the most upregulated and downregulated lncRNAs. Using quantitative real-time reverse transcription polymerase chain reaction (RT-QPCR), we confirmed the differential expression of three top upregulated and downregulated lncRNAs along with two other randomly picked lncRNAs. Gene Ontology (GO) and KEGG pathways analysis with these differentially expressed lncRNAs provide insight into the cellular pathway leading to LVNC pathogenesis. We also identified 1,066 upregulated and 1,017 downregulated mRNAs. Gene set enrichment analysis (GSEA) showed that G2M, Estrogen, and inflammatory pathways are enriched in differentially expressed genes (DEG). We also identified miRNA targets for these differentially expressed genes. In this study, we first report the use of LncRNA microarray to understand the pathogenesis of LVNC and to identify several lncRNA and genes and their targets as potential biomarkers.

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Section: Resultsmentioning

confidence: 99%

“…However, the roles of these pathways have not been extensively studied in relation to the development of LVNC ( 27 , 28 ). Furthermore, GSEA analysis identified HSPA1, DMD, and ADCY1 as having significant relevance in developing heart ailments and which presumably play a critical role in developing LVNC ( 32 , 34 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Tian

Niu

Liu

et al. 2021

Front. Cardiovasc. Med.

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“…Extensive review of the role metabolic enzymes and neuronal signaling genes play in alcohol behavior can be found elsewhere [31, 52, 124]. We will now highlight gene networks identified in the fly that have received less attention and will be crucial in understanding alcohol behavior across species [18, 100, 125–128].…”

Section: Part 2: Gene Network Implicated In Alcohol Behavior In the Flymentioning

confidence: 99%

“…Glial dysfunction and structural change as a consequence of alcohol consumption have been documented across species [100, 127] and glial involvement in alcohol behavior in the fly is not new. Early forward genetics screens showed disruptions in the blood brain barrier (BBB) leading to alcohol resistance [137].…”

Section: Part 2: Gene Network Implicated In Alcohol Behavior In the Flymentioning

confidence: 99%

Studying alcohol use disorder using Drosophila melanogaster in the era of ‘Big Data’

et al. 2019

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Our understanding of the networks of genes and protein functions involved in Alcohol Use Disorder (AUD) remains incomplete, as do the mechanisms by which these networks lead to AUD phenotypes. The fruit fly ( Drosophila melanogaster ) is an efficient model for functional and mechanistic characterization of the genes involved in alcohol behavior. The fly offers many advantages as a model organism for investigating the molecular and cellular mechanisms of alcohol-related behaviors, and for understanding the underlying neural circuitry driving behaviors, such as locomotor stimulation, sedation, tolerance, and appetitive (reward) learning and memory. Fly researchers are able to use an extensive variety of tools for functional characterization of gene products. To understand how the fly can guide our understanding of AUD in the era of Big Data we will explore these tools, and review some of the gene networks identified in the fly through their use, including chromatin-remodeling, glial, cellular stress, and innate immunity genes. These networks hold great potential as translational drug targets, making it prudent to conduct further research into how these gene mechanisms are involved in alcohol behavior.

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“…Loss of ADCY1 function might lead to drastically-behavioral impairments in sensorimotor and social behaviors 23. ADCY1 was also reported to be associated with alcohol addiction, and depression from adolescence to adult as well as in postpartum motherhood, which were accompanied by a down-regulation of ADCY1 expression 24, 25.…”

Section: Introductionmentioning

confidence: 99%

A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer

et al. 2019

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Adenylate cyclase 1 (ADCY1 or AC1) is a member of ADCY superfamily and was primarily found to be expressed in the brain. ADCY1 is responsible for catalyzing ATP to cyclic AMP (cAMP). As a secondary messenger, cAMP can regulate plenty of cellular activities. cAMP can perform its regulation in cellular transport through the binding to cAMP dependent protein kinases (PKAs), cAMP-activated guanine exchange factors (EPACs) and cyclic nucleotide-gated channels functioning in transduction of sensory signals (CNGs). Lung cancer is one of the leading factors of cancer-related death worldwide. Platinum-based chemotherapy is the first-line treatment for advanced lung cancer patients. In addition, surgical treatment, radiation treatment, and molecular targeted therapy are also therapeutic options for lung cancer patients in clinical settings. However, drug resistance and toxicity are the major obstacles that affect chemotherapy outcome and prognosis of lung cancer patients. And the therapeutic efficiency and adverse effects are varying with each individual. In recent years, investigations based on genetic sequencing have revealed the emerging role of ADCY1 mutations in affecting drug efficiency in various cancers such as lung cancer, esophageal cancer and colorectal cancer. The potential function of ADCY1 in chemotherapy resistance is of great importance to be noticed and investigated.

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Chronic alcohol consumption from adolescence-to-adulthood in mice - hypothalamic gene expression changes in the dilated cardiomyopathy signaling pathway

Cited by 12 publications

References 90 publications

Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

Studying alcohol use disorder using Drosophila melanogaster in the era of ‘Big Data’

A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer

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