scholarly journals The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinyan Wang ◽  
Lijuan Chen ◽  
Ping Qiang
Keyword(s):  
Rna Binding ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Cancer Prognosis ◽  
Messenger Rnas ◽  
Multiple Cancer ◽  
Multiple Cell ◽  
Mrna Binding ◽  
Post Transcriptional Regulation

AbstractThe human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.

scholarly journals Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses

2022 ◽  
Vol 12 ◽  
Author(s):  
Jinwu Peng ◽  
Qiuju Liang ◽  
Zhijie Xu ◽  
Yuan Cai ◽  
Bi Peng ◽  
...  
Keyword(s):  
Immune Regulation ◽  
Response Prediction ◽  
Cell Types ◽  
Clinicopathological Characteristics ◽  
The Novel ◽  
Multiple Cancer ◽  
Exosomal Mirnas ◽  
Multiple Cell ◽  
Almost All ◽  
Therapeutic Responses

Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.

scholarly journals Mutational signature SBS8 predominantly arises due to late replication errors in cancer

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Vinod Kumar Singh ◽  
Arnav Rastogi ◽  
Xiaoju Hu ◽  
Yaqun Wang ◽  
Subhajyoti De
Keyword(s):  
Dna Repair ◽  
Cancer Progression ◽  
Replication Timing ◽  
Cell Types ◽  
Late Replication ◽  
Multiple Cancer ◽  
Mutational Signatures ◽  
Replication Errors ◽  
Mutational Signature ◽  
Multiple Cell

AbstractAlthough a majority of somatic mutations in cancer are passengers, their mutational signatures provide mechanistic insights into mutagenesis and DNA repair processes. Mutational signature SBS8 is common in most cancers, but its etiology is debated. Incorporating genomic, epigenomic, and cellular process features for multiple cell-types we develop genome-wide composite epigenomic context-maps relevant for mutagenesis and DNA repair. Analyzing somatic mutation data from multiple cancer types in their epigenomic contexts, we show that SBS8 preferentially occurs in gene-poor, lamina-proximal, late replicating heterochromatin domains. While SBS8 is uncommon among mutations in non-malignant tissues, in tumor genomes its proportions increase with replication timing and speed, and checkpoint defects further promote this signature - suggesting that SBS8 probably arises due to uncorrected late replication errors during cancer progression. Our observations offer a potential reconciliation among different perspectives in the debate about the etiology of SBS8 and its relationship with other mutational signatures.

scholarly journals A Census and Categorization Method of Epitranscriptomic Marks

2020 ◽  
Vol 21 (13) ◽  
pp. 4684
Author(s):  
Julia Mathlin ◽  
Loredana Le Pera ◽  
Teresa Colombo
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Messenger Rnas ◽  
Rna Modifications ◽  
Chemical Modifications ◽  
Rna Molecules ◽  
Transcriptional Regulatory ◽  
Functional Relevance

In the past few years, thorough investigation of chemical modifications operated in the cells on ribonucleic acid (RNA) molecules is gaining momentum. This new field of research has been dubbed “epitranscriptomics”, in analogy to best-known epigenomics, to stress the potential of ensembles of RNA modifications to constitute a post-transcriptional regulatory layer of gene expression orchestrated by writer, reader, and eraser RNA-binding proteins (RBPs). In fact, epitranscriptomics aims at identifying and characterizing all functionally relevant changes involving both non-substitutional chemical modifications and editing events made to the transcriptome. Indeed, several types of RNA modifications that impact gene expression have been reported so far in different species of cellular RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, messenger RNAs, and long non-coding RNAs. Supporting functional relevance of this largely unknown regulatory mechanism, several human diseases have been associated directly to RNA modifications or to RBPs that may play as effectors of epitranscriptomic marks. However, an exhaustive epitranscriptome’s characterization, aimed to systematically classify all RNA modifications and clarify rules, actors, and outcomes of this promising regulatory code, is currently not available, mainly hampered by lack of suitable detecting technologies. This is an unfortunate limitation that, thanks to an unprecedented pace of technological advancements especially in the sequencing technology field, is likely to be overcome soon. Here, we review the current knowledge on epitranscriptomic marks and propose a categorization method based on the reference ribonucleotide and its rounds of modifications (“stages”) until reaching the given modified form. We believe that this classification scheme can be useful to coherently organize the expanding number of discovered RNA modifications.

scholarly journals Exosomes: A New Pathway for Cancer Drug Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Yunbin Zhong ◽  
Haibo Li ◽  
Peiwen Li ◽  
Yong Chen ◽  
Mengyao Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Current Knowledge ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
Tumor Drug Resistance ◽  
Cells Of Origin ◽  
Potential Applications ◽  
Multiple Cell

Exosomes are extracellular vesicles (EVs) that are secreted into body fluids by multiple cell types and are enriched in bioactive molecules, although their exact contents depend on the cells of origin. Studies have shown that exosomes in the tumor microenvironment affect tumor growth, metastasis and drug resistance by mediating intercellular communication and the transport of specific molecules, although their exact mechanisms of action need to be investigated further. In this review, we have summarized current knowledge on the relationship between tumor drug resistance and exosomes, and have discussed the potential applications of exosomes as diagnostic biomarkers and therapeutic targets.

scholarly journals Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

2021 ◽  
Vol 22 (23) ◽  
pp. 13068
Author(s):  
Giovanni Tulipano
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Level ◽  
Endocrine Tumors ◽  
Age Related ◽  
Distinct Cell ◽  
First Choice ◽  
Integrated Or

Metformin is considered the first-choice drug for type 2 diabetes treatment. Actually, pleiotropic effects of metformin have been recognized, and there is evidence that this drug may have a favorable impact on health beyond its glucose-lowering activity. In summary, despite its long history, metformin is still an attractive research opportunity in the field of endocrine and metabolic diseases, age-related diseases, and cancer. To this end, its mode of action in distinct cell types is still in dispute. The aim of this work was to review the current knowledge and recent findings on the molecular mechanisms underlying the pharmacological effects of metformin in the field of metabolic and endocrine pathologies, including some endocrine tumors. Metformin is believed to act through multiple pathways that can be interconnected or work independently. Moreover, metformin effects on target tissues may be either direct or indirect, which means secondary to the actions on other tissues and consequent alterations at systemic level. Finally, as to the direct actions of metformin at cellular level, the intracellular milieu cooperates to cause differential responses to the drug between distinct cell types, despite the primary molecular targets may be the same within cells. Cellular bioenergetics can be regarded as the primary target of metformin action. Metformin can perturb the cytosolic and mitochondrial NAD/NADH ratio and the ATP/AMP ratio within cells, thus affecting enzymatic activities and metabolic and signaling pathways which depend on redox- and energy balance. In this context, the possible link between pyruvate metabolism and metformin actions is extensively discussed.

scholarly journals PPAR and Agonists against Cancer: Rational Design of Complementation Treatments

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-13 ◽  
Author(s):  
Dorina Veliceasa ◽  
Frank Thilo Schulze-Hoëpfner ◽  
Olga V. Volpert
Keyword(s):  
Rational Design ◽  
Current Knowledge ◽  
Vascular Complications ◽  
Recent Decade ◽  
Cell Types ◽  
Insulin Sensitizers ◽  
Ppar Agonists ◽  
Multiple Cell

PPAR is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPAR has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPAR role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPAR image as potential anticancer drug. Currently PPAR is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, however, identify pro-angiogenic and tumor-promoting effects of PPAR and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPAR regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPAR agonists.

Transcriptional regulation of early cardiovascular development

2018 ◽  
Author(s):  
F. Gabriella Fulcoli ◽  
Antonio Baldini
Keyword(s):  
Transcription Factors ◽  
Current Knowledge ◽  
Cell Types ◽  
Regulatory Elements ◽  
Developmental Time ◽  
Special Focus ◽  
Cardiovascular Development ◽  
Cardiac Progenitors ◽  
Multiple Cell

The two major cardiac cell lineages of the vertebrate heart, the first and second cardiac fields (FHF and SHF), have different developmental ontogeny and thus different transcription programs. Most remarkably, the fate of cardiac progenitors (CPs) of the FHF is restricted to cardiomyocyte differentiation. In contrast, SHF CPs, which are specified independently, are maintained in a multipotent state for a relatively longer developmental time and can differentiate into multiple cell types. The identity of the transcription factors and regulatory elements involved in progenitor cell programming and fate are only now beginning to emerge. Apparent inconsistencies between studies based on tissue culture and in vivo embryonic studies confirm that the ontogeny of cardiac progenitors is strongly driven or affected by regionalization, and thus by the signals that they receive in different regions. This chapter summarizes current knowledge about transcription factors and mechanisms driving CP ontogeny, with special focus on SHF development.

Nucleolin Interacts and Co-Localizes with Components of Pre-Catalytic Spliceosome Complexes

Sci ◽  
2019 ◽  
Vol 1 (2) ◽  
pp. 33 ◽  
Author(s):  
Iva Ugrinova ◽  
Mounira Chalabi-Dchar ◽  
Karine Monier ◽  
Philippe Bouvet
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosomal Rna ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Interacting Proteins ◽  
Messenger Rnas ◽  
Nuclear Speckles ◽  
Post Transcriptional Regulation ◽  
Rna Polymerase Ii Transcription

Nucleolin is an RNA binding protein that is involved in many post-transcriptional regulation steps of messenger RNAs in addition to its nucleolar role in ribosomal RNA transcription and assembly in pre-ribosomes. Acetylated nucleolin was found to be associated with nuclear speckles and to co-localize with the splicing factor SC35. Previous nuclear pull down of nucleolin identified several splicing components and factors involved in RNA polymerase II transcription associated with nucleolin. In this report, we show that these splicing components are specifics of the pre-catalytic A and B spliceosomes, while proteins recruited in the Bact, C and P complexes are absent from the nucleolin interacting proteins. Furthermore, we show that acetylated nucleolin co-localized with P-SF3B1, a marker of co-transcriptional active spliceosomes. P-SF3B1 complexes can be pulled down with nucleolin specific antibodies. Interestingly, the alternative splicing of Fibronectin at the IIICS and EDB sites was affected by nucleolin depletion. These data are consistent with a model where nucleolin could be a factor bridging RNA polymerase II transcription and assembly of pre-catalytic spliceosome similarly to its function in the co-transcriptional maturation of pre-rRNA.

scholarly journals The Role of Exosomes in Bone Remodeling: Implications for Bone Physiology and Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Christos Masaoutis ◽  
Stamatios Theocharis
Keyword(s):  
Bone Remodeling ◽  
Current Knowledge ◽  
Active Role ◽  
Cell Types ◽  
Matrix Mineralization ◽  
Physiological Phenomenon ◽  
Health And Disease ◽  
Multiple Cell ◽  
Bone Physiology

Bone remodeling represents a physiological phenomenon of continuous bone tissue renewal that requires fine orchestration of multiple cell types, which is critical for the understanding of bone disease but not yet clarified in precise detail. Exosomes, which are cell-secreted nanovesicles drawing increasing attention for their broad biosignaling functions, can shed new light on how multiple heterogeneous cells communicate for the purpose of bone remodeling. In the healthy bone, exosomes transmit signals favoring both bone synthesis and resorption, regulating the differentiation, recruitment, and activity of most cell types involved in bone remodeling and even assuming an active role in extracellular matrix mineralization. Additionally, in the ailing bone, they actively participate in pathogenic processes constituting also potential therapeutic agents and drug vectors. The present review summarizes the current knowledge on bone exosomes and bone remodeling in health and disease.

scholarly journals Regulation of Fetal Genes by Transitions among RNA-Binding Proteins during Liver Development

2020 ◽  
Vol 21 (23) ◽  
pp. 9319
Author(s):  
Toru Suzuki ◽  
Shungo Adachi ◽  
Chisato Kikuguchi ◽  
Shinsuke Shibata ◽  
Saori Nishijima ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fetal Liver ◽  
Regulatory Protein ◽  
Rna Decay ◽  
Translation Efficiency ◽  
Mrna Binding ◽  
Post Transcriptional Regulation

Transcripts of alpha-fetoprotein (Afp), H19, and insulin-like growth factor 2 (Igf2) genes are highly expressed in mouse fetal liver, but decrease drastically during maturation. While transcriptional regulation of these genes has been well studied, the post-transcriptional regulation of their developmental decrease is poorly understood. Here, we show that shortening of poly(A) tails and subsequent RNA decay are largely responsible for the postnatal decrease of Afp, H19, and Igf2 transcripts in mouse liver. IGF2 mRNA binding protein 1 (IMP1), which regulates stability and translation efficiency of target mRNAs, binds to these fetal liver transcripts. When IMP1 is exogenously expressed in mouse adult liver, fetal liver transcripts show higher expression and possess longer poly(A) tails, suggesting that IMP1 stabilizes them. IMP1 declines concomitantly with fetal liver transcripts as liver matures. Instead, RNA-binding proteins (RBPs) that promote RNA decay, such as cold shock domain containing protein E1 (CSDE1), K-homology domain splicing regulatory protein (KSRP), and CUG-BP1 and ETR3-like factors 1 (CELF1), bind to 3′ regions of fetal liver transcripts. These data suggest that transitions among RBPs associated with fetal liver transcripts shift regulation from stabilization to decay, leading to a postnatal decrease in those fetal transcripts.

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