Roles of M6A Regulators in Hepatocellular Carcinoma: Promotion or Suppression

2021 ◽  
Vol 21 ◽  
Author(s):  
Jiamao Chen ◽  
Qian Zhang ◽  
Ting Liu ◽  
Hua Tang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Clinical Treatment ◽  
Self Renewal ◽  
Regulate Gene Expression ◽  
Regulate Gene

: Hepatocellular carcinoma (HCC) is the sixth globally diagnosed cancer with a poor prognosis. Although the pathological factors of hepatocellular carcinoma are well elucidated, the underlying molecular mechanisms remain unclear. N6-methyladenosine (m6A) is an adenosine methylation occurring at the N6 site, which is the most prevalent modification of eukaryotic mRNA. Recent studies have shown that m6A can regulate gene expression, thus modulating the processes of cell self-renewal, differentiation, and apoptosis. The methyls in m6A are installed by methyltransferases (“writers”), removed by demethylases (“erasers”) and recognized by m6A-binding proteins (“readers”). In this review, we discuss the roles of above regulators in the progression and prognosis of HCC, and summarize the clinical association between m6A modification and hepatocellular carcinoma, so as to provide more valuable information for clinical treatment.

scholarly journals Functional Identification of MicroRNA-Centered Complexes in C. Elegans.

2022 ◽  
Author(s):  
Shilpa Hebbar ◽  
Ganesh Panzade ◽  
Ajay Vashisht ◽  
James Wohlschlegel ◽  
Isana Veksler-Lublinsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mass Spectrometry Analysis ◽  
Functional Identification ◽  
Regulate Gene Expression ◽  
Mutant Phenotypes ◽  
Regulate Gene

Abstract microRNAs (miRNAs) are crucial for normal development and physiology. To identify factors that might coordinate with miRNAs to regulate gene expression, we used 2’-O methylated oligonucleotides to precipitate Caenorhabditis elegans let-7, miR-58, and miR-2 miRNAs and the associated proteins. A total of 211 proteins were identified through mass-spectrometry analysis of miRNA co-precipitates, which included previously identified interactors of key miRNA pathway components. Gene ontology analysis of the identified interactors revealed an enrichment for RNA binding proteins, suggesting that we captured proteins that may be involved in mRNA lifecycle. To determine which miRNA interactors are important for miRNA activity, we used RNAi to deplete putative miRNA co-factors in animals with compromised miRNA activity and looked for alterations of the miRNA mutant phenotypes. Depletion of 25 of 39 tested genes modified the miRNA mutant phenotypes in three sensitized backgrounds. Modulators of miRNA phenotypes ranged from RNA binding proteins RBD-1 and CEY-1 to metabolic factors such as DLST-1 and ECH-5, among others. The observed functional interactions suggest widespread coordination of these proteins with miRNAs to ultimately regulate gene expression. This study provides a foundation for future investigations aimed at deciphering the molecular mechanisms of miRNA-mediated gene regulation.

scholarly journals Growing Evidence of Exosomal MicroRNA-Related Metastasis of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Wenbing Sun ◽  
Shuqi Fu ◽  
Size Wu ◽  
Rong Tu
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cause Of Death ◽  
Distant Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Regulate Gene Expression ◽  
Mesenchymal Transition ◽  
Exosomal Microrna ◽  
Regulate Gene

Metastasis is the prominent cause of death in patients with hepatocellular carcinoma (HCC); however, the mechanisms behind HCC metastasis are not well understood. MicroRNAs (miRs) can regulate gene expression and affect HCC metastasis. Exosomes can transport miRs and other cargoes to and from different cells, thus being associated with tumour-distant metastasis. Exosomal miRs involve different processes of HCC metastasis through their functional effects, such as their induction of epithelial-to-mesenchymal transition, angiogenesis, and distant niche. In this review, data from the literature were analysed and summarised, with a focus on the evidence extraction of exosomal miRs in HCC metastasis with the purpose of increasing the understanding of the mechanisms behind HCC metastasis and acquiring implications for application.

scholarly journals KH domain containing RNA-binding proteins coordinate with microRNAs to regulate Caenorhabditis elegans development

2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Dustin Haskell ◽  
Anna Zinovyeva
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulate Gene Expression ◽  
C Elegans ◽  
Binding Domains ◽  
Kh Domain ◽  
Regulate Gene

Abstract MicroRNAs (miRNAs) and RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate their activities and the precise mechanisms of this coordination are not well understood. RBPs often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa-1 and asd-2, genetically interacted with all of the miRNA mutants tested, whereas other KH domain genes showed genetic interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators.

scholarly journals Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 813 ◽  
Author(s):  
Amelia R. I. Lindsey
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Promising Candidate ◽  
Regulate Gene Expression ◽  
Host Interaction ◽  
Female Germline ◽  
Intracellular Infections ◽  
Regulate Gene

Wolbachia (Anaplasmataceae) is an endosymbiont of arthropods and nematodes that resides within host cells and is well known for manipulating host biology to facilitate transmission via the female germline. The effects Wolbachia has on host physiology, combined with reproductive manipulations, make this bacterium a promising candidate for use in biological- and vector-control. While it is becoming increasingly clear that Wolbachia’s effects on host biology are numerous and vary according to the host and the environment, we know very little about the molecular mechanisms behind Wolbachia’s interactions with its host. Here, I analyze 29 Wolbachia genomes for the presence of systems that are likely central to the ability of Wolbachia to respond to and interface with its host, including proteins for sensing, signaling, gene regulation, and secretion. Second, I review conditions under which Wolbachia alters gene expression in response to changes in its environment and discuss other instances where we might hypothesize Wolbachia to regulate gene expression. Findings will direct mechanistic investigations into gene regulation and host-interaction that will deepen our understanding of intracellular infections and enhance applied management efforts that leverage Wolbachia.

scholarly journals KH domain containing RNA-binding proteins coordinate with microRNAs to regulate Caenorhabditis elegans development

2020 ◽  
Author(s):  
D Haskell ◽  
A Zinovyeva
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulate Gene Expression ◽  
C Elegans ◽  
Binding Domains ◽  
Kh Domain ◽  
Regulate Gene

ABSTRACTmicroRNAs (miRNAs) and RNA binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate and the precise mechanisms of their coordination are not well understood. RNA binding proteins often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K Homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa-1 and asd-2, genetically interacted with all of the miRNA mutants tested, while other KH domain genes exhibited functional interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators.

scholarly journals An independent poor-prognosis subtype of hepatocellular carcinoma based on the tumor microenvironment

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098064
Author(s):  
Junfeng Wang ◽  
Jianying Lou ◽  
Lei Fu ◽  
Qu Jin
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Using Data

Background Hepatocellular carcinoma (HCC) is a highly malignant tumor with a particularly poor prognosis. The tumor microenvironment (TME) is closely associated with tumorigenesis, progression, and treatment. However, the relationship between TME genes and HCC patient prognosis is poorly understood. Methods In this study, we identified two prognostic subtypes based on the TME using data from The Cancer Genome Atlas and Gene Expression Omnibus. The Microenvironment Cell Populations-counter method was used to evaluate immune cell infiltration in HCC. Differentially expressed genes between molecular subtypes were calculated with the Limma package, and clusterProfiler was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to identify genes related to the independent subtypes. We also integrated mRNA expression data into our bioinformatics analysis. Results We identified 4227 TME-associated genes and 640 genes related to the prognosis of HCC. We defined two major subtypes (Clusters 1 and 2) based on the analysis of TME-associated gene expression. Cluster 1 was characterized by increased expression of immune-associated genes and a worse prognosis than Cluster 2. Conclusions The identification of these HCC subtypes based on the TME provides further insight into the molecular mechanisms and prediction of HCC prognosis.

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