Critical functions of lncRNA DGCR5 in cancers of the digestive system

2021 ◽  
Vol 27 ◽  
Author(s):  
Chengyu Hu ◽  
Wen Xu ◽  
Bei Wang ◽  
Jinlan Chen ◽  
Zixian Zhou ◽  
...  
Keyword(s):  
Digestive System ◽  
Molecular Mechanisms ◽  
Ductal Adenocarcinoma ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Reading Frame ◽  
Promising Therapeutic Target ◽  
Digestive Cancers ◽  
Pathological Development

Background: Long non-coding RNAs (lncRNAs) has no protein-coding potential due to the lack of an apparent open reading frame. There is growing evidence that lncRNA DGCR5 has a vital regulatory role in human illnesses' pathological development, particularly in the digestive system's carcinogenesis and progression. Abnormal DGCR5 expression affects different cellular functions such as proliferation, aggression, and metastasis. This paper aims to probe into the pathophysiological functions and molecular mechanisms of DGCR5 in cancers of the digestive system. Methods: This review summarizes and analyzes the biological functions and mechanisms of lncRNA DGCR5 in digestive system cancers occurrence. Relevant studies were conducted and reviewed by searching PubMed for articles with lncRNA DGCR5 and digestive system cancer as keywords in recent years. Results: DCGR5, as a novel tumor-related lncRNA, is recently identified to be abnormally expressed in digestive system cancers, such as pancreatic ductal adenocarcinoma, pancreatic cancer, gastric cancer, gallbladder cancer, colorectal cancer, and hepatocellular carcinoma. The role played by DCGR5 is vital and varies in different digestive cancers. Taken together, aberrant expression of DCGR5 regulates the progression of digestive cancers by affecting cancer cell proliferation, aggression, metastasis, and drug resistance. Conclusion: LncRNA DGCR5 might be a viable marker or a promising therapeutic target in digestive system cancers.

scholarly journals Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Yalu Zhang ◽  
Qiaofei Liu ◽  
Quan Liao
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Cellular Functions ◽  
Immune Microenvironment ◽  
Protein Coding ◽  
Functional Roles ◽  
Tumor Immune Microenvironment

Abstract Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations.

scholarly journals Convergent and distributed effects of the schizophrenia-associated 3q29 deletion on the human neural transcriptome

2020 ◽  
Author(s):  
Esra Sefik ◽  
Ryan H. Purcell ◽  
Elaine F. Walker ◽  
Gary J. Bassell ◽  
Jennifer G. Mulle ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Single Gene ◽  
Normal Function ◽  
Cellular Functions ◽  
Protein Coding ◽  
Post Translational Modifications ◽  
Increased Risk ◽  
Disease Associations ◽  
Guilt By Association ◽  
The Impact

AbstractThe 3q29 deletion (3q29Del) confers >40-fold increased risk for schizophrenia. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, post-translational modifications, chromatin remodeling and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological post-mortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.

scholarly journals Construction the first gene co-expression-based interactome in cattle

2017 ◽  
Author(s):  
Yan Chen ◽  
Yining Liu ◽  
Min Du ◽  
Wengang Zhang ◽  
Xue Gao ◽  
...  
Keyword(s):  
Dna Binding ◽  
Rna Polymerase Ii ◽  
Complex Traits ◽  
Molecular Mechanisms ◽  
Meat Production ◽  
Regulation Of Transcription ◽  
Cattle Genome ◽  
Cellular Functions ◽  
Protein Coding ◽  
Important Approach

Integrating genomic information into cattle breeding is an important approach to exploring the molecular mechanism for complex traits related to diary and meat production. To assist with genomic-based selection, a reference map of interactome is needed to fully understand genotype-phenotype relationships. To this end we constructed a co-expression analysis of 92 tissues and this represents the first systematic exploration of gene-gene relationship in cattle. By using robust WGCNA (Weighted Gene Correlation Network Analysis), we described the gene co-expression network of 13,405 protein-coding genes from the cattle genome. Using the 5,000 genes with majority variations in expression across 92 tissues, we compiled a network with 72,306 co-associations and that provides functional insights into thousands of poorly characterized proteins. Further module identifications found 55 highly organized functional clusters representing diverse cellular activities. To demonstrate the re-use of our interaction for functional genomics analysis, we extracted a sub-network associated with DNA binding genes in cattle. The subnetwork was enriched within regulation of transcription from RNA polymerase II promoter representing central cellular functions. In addition, we identified 28 novel linker genes associated with more than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction will be a valuable resource for exploring the molecular mechanisms of incompletely characterized proteins and for elucidating larger-scale patterns of functional modulization in the cattle genome.

scholarly journals LncRNAs as Chromatin Regulators in Cancer: From Molecular Function to Clinical Potential

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1524 ◽  
Author(s):  
Rodiola Begolli ◽  
Nikos Sideris ◽  
Antonis Giakountis
Keyword(s):  
High Throughput Sequencing ◽  
Specific Gene ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Chromatin Regulators ◽  
Epigenetic Machinery ◽  
Altered Gene ◽  
Epigenetic Disruption ◽  
Clinical Potential

During the last decade, high-throughput sequencing efforts in the fields of transcriptomics and epigenomics have shed light on the noncoding part of the transcriptome and its potential role in human disease. Regulatory noncoding RNAs are broadly divided into short and long noncoding transcripts. The latter, also known as lncRNAs, are defined as transcripts longer than 200 nucleotides with low or no protein-coding potential. LncRNAs form a diverse group of transcripts that regulate vital cellular functions through interactions with proteins, chromatin, and even RNA itself. Notably, an important regulatory aspect of these RNA species is their association with the epigenetic machinery and the recruitment of its regulatory apparatus to specific loci, resulting in DNA methylation and/or post-translational modifications of histones. Such epigenetic modifications play a pivotal role in maintaining the active or inactive transcriptional state of chromatin and are crucial regulators of normal cellular development and tissue-specific gene expression. Evidently, aberrant expression of lncRNAs that interact with epigenetic modifiers can cause severe epigenetic disruption and is thus is closely associated with altered gene function, cellular dysregulation, and malignant transformation. Here, we survey the latest breakthroughs concerning the role of lncRNAs interacting with the epigenetic machinery in various forms of cancer.

scholarly journals Convergent and distributed effects of the 3q29 deletion on the human neural transcriptome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esra Sefik ◽  
Ryan H. Purcell ◽  
Katrina Aberizk ◽  
Hallie Averbach ◽  
Emily Black ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Single Gene ◽  
Normal Function ◽  
Cellular Functions ◽  
Protein Coding ◽  
Risk Genes ◽  
Disease Associations ◽  
Guilt By Association ◽  
The Impact

AbstractThe 3q29 deletion (3q29Del) confers high risk for schizophrenia and other neurodevelopmental and psychiatric disorders. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, posttranslational modifications, chromatin remodeling, and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism, and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological postmortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.

scholarly journals Pathophysiological Role of K2P Channels in Human Diseases

2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Ion Homeostasis ◽  
Human Diseases ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
K2p Channels ◽  
And Function

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

scholarly journals Functional Evaluation of KEL As An Oncogenic Gene in The Progression of Acute Erythroleukemia

2021 ◽  
Author(s):  
Zijuan Wu ◽  
Wenjie Liu ◽  
Yan Yu ◽  
Chun Qiao ◽  
Han Zhu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Biological Significance ◽  
Erythroid Differentiation ◽  
Regulation Mechanism ◽  
Functional Evaluation ◽  
Aberrant Expression ◽  
Promising Therapeutic Target ◽  
Luciferase Activity Assay

Abstract Background Acute erythroleukemia (AEL) is an infrequent subtype of acute myeloid leukemia (AML) with worse prognosis. Though the last decade has seen major advances in the novel features and genomic landscape in AEL, there is still a lack of specific therapeutic targets and effective treatment approaches for this disease. MethodsTCGA database was used to screen out the oncogene with specifically aberrant expression in AEL. Protein array was performed to explore the activated signaling pathways and targets that undergo phosphorylation modulation. A series of functional analyses in cell lines and mice models were performed to investigate the biological significance and clinical relevance of KEL regulation in AEL. CHIP, EMSA and dual-luciferase activity assay were performed to explore the upstream regulation mechanism of KEL.ResultsIn this study, the results showed that KEL promoted cell proliferation and its downregulation reversed drug resistance in AEL cells to JQ1. Our findings suggested that KEL contributed to gain of H3K27 acetylation and promoted erythroid differentiation induced by GATA1. Additionally, GATA1 and TAL1 as co-Transcription factors (TFs) modulated the expression of KEL. Maintaining cell viability and differentiation, KEL also played parts in the immune evasion of tumor cells. ConclusionsOur work expands the current knowledge regarding molecular mechanisms involved in cancer onset and progression, offering promising therapeutic target to broaden the treatment options.

scholarly journals Construction the first gene co-expression-based interactome in cattle

2017 ◽  
Author(s):  
Yan Chen ◽  
Yining Liu ◽  
Min Du ◽  
Wengang Zhang ◽  
Xue Gao ◽  
...  
Keyword(s):  
Dna Binding ◽  
Rna Polymerase Ii ◽  
Complex Traits ◽  
Molecular Mechanisms ◽  
Meat Production ◽  
Regulation Of Transcription ◽  
Cattle Genome ◽  
Cellular Functions ◽  
Protein Coding ◽  
Important Approach

Integrating genomic information into cattle breeding is an important approach to exploring the molecular mechanism for complex traits related to diary and meat production. To assist with genomic-based selection, a reference map of interactome is needed to fully understand genotype-phenotype relationships. To this end we constructed a co-expression analysis of 92 tissues and this represents the first systematic exploration of gene-gene relationship in cattle. By using robust WGCNA (Weighted Gene Correlation Network Analysis), we described the gene co-expression network of 13,405 protein-coding genes from the cattle genome. Using the 5,000 genes with majority variations in expression across 92 tissues, we compiled a network with 72,306 co-associations and that provides functional insights into thousands of poorly characterized proteins. Further module identifications found 55 highly organized functional clusters representing diverse cellular activities. To demonstrate the re-use of our interaction for functional genomics analysis, we extracted a sub-network associated with DNA binding genes in cattle. The subnetwork was enriched within regulation of transcription from RNA polymerase II promoter representing central cellular functions. In addition, we identified 28 novel linker genes associated with more than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction will be a valuable resource for exploring the molecular mechanisms of incompletely characterized proteins and for elucidating larger-scale patterns of functional modulization in the cattle genome.

scholarly journals MicroRNAs: Recent insights towards their role in male infertility and reproductive cancers

2019 ◽  
Vol 19 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Muhammad Babar Khawar ◽  
Rabia Mehmood ◽  
Nabila Roohi
Keyword(s):  
Male Infertility ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Reproductive Cancers ◽  
Post Transcriptional Regulation ◽  
Different Cell Types

Spermatogenesis is a tightly controlled, multi-step process in which mature spermatozoa are produced. Disruption of regulatory mechanisms in spermatogenesis can lead to male infertility, various diseases of male reproductive system, or even cancer. The spermatogenic impairment in infertile men can be associated with different etiologies, and the exact molecular mechanisms are yet to be determined. MicroRNAs (miRNAs) are a type of non-protein coding RNAs, about 22 nucleotides long, with an essential role in post-transcriptional regulation. miRNAs have been recognized as important regulators of various biological processes, including spermatogenesis. The aim of this review is to summarize the recent literature on the role of miRNAs in spermatogenesis, male infertility and reproductive cancers, and to evaluate their potential in diagnosis, prognosis and therapy of disease. Experimental evidence shows that aberrant expression of miRNAs affects spermatogenesis at multiple stages and in different cell types, most often resulting in infertility. In more severe cases, dysregulation of miRNAs leads to cancer. miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and reproductive system diseases. However, to exploit this potential fully, we need a better understanding of miRNA-mediated regulation of spermatogenesis, including the characterization of yet unidentified miRNAs and related regulatory mechanisms.

scholarly journals BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells

2017 ◽  
Vol 216 (12) ◽  
pp. 4091-4105 ◽  
Author(s):  
Ming-Xin An ◽  
Si Li ◽  
Han-Bing Yao ◽  
Chao Li ◽  
Jia-Mei Wang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Aerobic Glycolysis ◽  
Ductal Adenocarcinoma ◽  
Aberrant Expression ◽  
Hexokinase 2 ◽  
Pancreatic Cancer Cells

Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents.

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