Emerging roles for ncRNAs in alcohol use disorders

Mayfield, R. Dayne

doi:10.1016/j.alcohol.2017.01.004

Cited by 41 publications

(40 citation statements)

References 95 publications

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“…These data suggest that serum GATA6-AS level may be used for the diagnosis of cervical squamous cell carcinoma. It is understood that the expression of certain lncRNAs is affected by various factors, including aging (21), alcohol consumption (22) and tobacco abuse (23). In the present study, serum levels of GATA6-AS demonstrated no significant association with age, drinking habit or smoking habit, which indicates the high stability of serum GATA6-AS as a potential biomarker of disease.…”

Section: Discussioncontrasting

confidence: 60%

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

et al. 2019

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The diagnosis and treatment of cervical squamous cell carcinoma is challenged by difficulties in the determination of tumor invasion. GATA binding protein 6 antisense (GATA6-AS) is a recently identified long non-coding RNA that exhibits critical functions in the growth of endothelial cells; however, to the best of our knowledge, its involvement in other physiological and pathological processes is unknown. By reverse transcription-quantitative polymerase chain reaction, the present study examined the expression of GATA6-AS in tumor tissues and adjacent healthy tissues, and the serum from patients with cervical squamous cell carcinoma and healthy controls. The diagnostic and prognostic potentials of GATA6-AS for cervical squamous cell carcinoma were analyzed by receiver operating characteristic curve analysis and survival curve analysis, respectively. Associations between the serum levels of GATA6-AS and clinical characteristics of patients with cervical squamous cell carcinoma were analyzed by a χ 2 test. A GATA6-AS overexpression vector was transfected into cervical squamous cell carcinoma cells, and the effects on cell migration and invasion were investigated by Transwell migration and invasion assays, respectively. The expression of mitogen-activated protein kinase kinase 4 (MTK-1) following transfection with the GATA6-AS overexpression vector was detected by western blot analysis. It was identified that the expression levels of GATA6-AS were lower in tumor tissues compared with healthy tissues. In addition, serum levels of GATA6-AS were higher in patients compared with healthy controls. The serum levels of GATA6-AS were associated with tumor metastasis, and may serve as a potential diagnostic and prognostic marker for cervical squamous cell carcinoma. Furthermore, GATA6-AS overexpression inhibited cancer cell migration and invasion. The expression levels of MTK-1 were also reduced following GATA6-AS overexpression. Therefore, the present study proposed that downregulated GATA6-AS expression was associated with tumor metastasis in cervical squamous cell carcinoma, and that GATA6-AS expression may inhibit cancer cell migration and invasion by downregulating MTK-1.

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Section: Discussioncontrasting

confidence: 60%

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

et al. 2019

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“…Although this cross‐sectional study only used self‐reported alcohol consumption, and only 3 Caucasian and 13 African men volunteered for this study, animal studies have partly confirmed this effect . More specifically, animal data indicate the complexity of epigenetic changes, not only involving methylation alterations, but also altered chromatin remodeling and different classes of non‐coding RNAs (ncRNAs) …”

Section: Does the Environment Influence Male Fertility And Sperm Charmentioning

confidence: 94%

Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?

Soubry

2017

BioEssays

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What are the effects of our environment on human development and the next generation? Numerous studies have provided ample evidence that a healthy environment and lifestyle of the mother is important for her offspring. Biological mechanisms underlying these environmental influences have been proposed to involve alterations in the epigenome. Is there enough evidence to suggest a similar contribution from the part of the father? Animal models provide proof of a transgenerational epigenetic effect through the paternal germ line, but can this be translated to humans? To date, literature on fathers is scarce. Human studies do not always incorporate appropriate tools to evaluate paternal influences or epigenetic effects. In reviewing the literature, I stress the need to explore and recognize paternal contributions to offspring's health within the Developmental Origins of Health and Disease hypothesis, and coin this new concept the Paternal Origins of Health and Disease paradigm (POHaD). A better understanding of preconceptional origins of disease through the totality of paternal exposures, or the paternal exposome, will provide evidence-based public health recommendations for future fathers.

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“…Bulk and scRNA-seq studies often exclude non-coding RNAs from their analyses (3,8,35) . However, the importance of ncRNAs is becoming increasingly apparent, not only in alcohol dependence (36) , but in brain physiology in general (37) , and these RNAs were therefore included in our data.…”

Section: Differential Expression and Pathway Analysismentioning

confidence: 99%

Single cell transcriptome profiling of the human alcohol-dependent brain

Brenner

Tiwari

Liu

et al. 2019

Preprint

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BackgroundAlcoholism remains a prevalent health concern throughout the world. Previous studies have identified transcriptomic patterns in the brain associated with alcohol dependence in both humans and animal models.But none of these studies have systematically investigated expression within the unique cell types present in the brain. ResultsWe utilized single nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of over 16,000 nuclei isolated from prefrontal cortex of alcoholic and control individuals. Each nucleus was assigned to one of seven major cell types by unsupervised clustering. Cell type enrichment patterns varied greatly among neuroinflammatory-related genes, which are known to play roles in alcohol dependence and neurodegeneration. Differential expression analysis identified cell type-specific genes with altered expression in alcoholics. The largest number of differentially expressed genes (DEGs), including both protein-coding and non-coding, were detected in astrocytes, oligodendrocytes, and microglia. ConclusionsTo our knowledge, this is the first single cell transcriptome analysis of alcohol-associated gene expression in any species, and the first such analysis in humans for any addictive substance. These findings greatly advance understanding of transcriptomic changes in the brain of alcohol-dependent individuals.1 Background Alcohol abuse is involved in over 200 pathologies and health conditions (e.g. alcohol dependence, liver cirrhosis, cancers, and injuries) and creates substantial social and economic burdens (1,2) . To develop more effective therapeutic strategies, we must first understand how alcohol affects the body at the cellular and molecular level. Previous studies of transcriptomic responses in human alcoholics (3-6) relied on RNA extracted from brain regions using tissue homogenates comprised of multiple cell types. This approach likely masks differences in gene expression patterns among specific cells, as well as heterogeneity from cell-to-cell variation within a given cell type.Single cell RNA sequencing (scRNA-seq) has recently gained attention in cell and molecular biology research for its ability to profile novel cell types and measure cell-to-cell variation in gene expression. To our knowledge, transcriptomic responses to chronic alcohol exposure or any other abused drug have not been studied at the cellular level in the human brain. We hypothesized that cell type-specific gene expression patterns associated with alcoholism will identify novel alcohol targets that were previously missed by bulk analysis of tissue homogenates, as has been shown for other neuropathologies (7,8) . Using single nucleus RNA-seq (snRNA-seq), a popular scRNA-seq alternative for analyzing frozen brain tissue (9-18) , we profiled the transcriptomes of 16,305 nuclei extracted from frozen prefrontal cortex (PFC) samples of 4 control and 3 alcohol dependent individuals. The PFC is involved in executive function and is an important substrate in the reward circuitry associated with development of a...

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Emerging roles for ncRNAs in alcohol use disorders

Cited by 41 publications

References 95 publications

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?

Single cell transcriptome profiling of the human alcohol-dependent brain

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