Developmental Roles of FUSE Binding Protein 1 (Fubp1) in Tooth Morphogenesis

FUSE binding protein 1 (Fubp1), a regulator of the c-Myc transcription factor and a DNA/RNA-binding protein, plays important roles in the regulation of gene transcription and cellular physiology. In this study, to reveal the precise developmental function of Fubp1, we examined the detailed expression pattern and developmental function of Fubp1 during tooth morphogenesis by RT-qPCR, in situ hybridization, and knock-down study using in vitro organ cultivation methods. In embryogenesis, Fubp1 is obviously expressed in the enamel organ and condensed mesenchyme, known to be important for proper tooth formation. Knocking down Fubp1 at E14 for two days, showed the altered expression patterns of tooth development related signalling molecules, including Bmps and Fgf4. In addition, transient knock-down of Fubp1 at E14 revealed changes in the localization patterns of c-Myc and cell proliferation in epithelium and mesenchyme, related with altered tooth morphogenesis. These results also showed the decreased amelogenin and dentin sialophosphoprotein expressions and disrupted enamel rod and interrod formation in one- and three-week renal transplanted teeth respectively. Thus, our results suggested that Fubp1 plays a modulating role during dentinogenesis and amelogenesis by regulating the expression pattern of signalling molecules to achieve the proper structural formation of hard tissue matrices and crown morphogenesis in mice molar development.

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Signaling Modulations of miR-206-3p in Tooth Morphogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms21155251 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5251

Author(s):

Sanjiv Neupane ◽

Yam Prasad Aryal ◽

Tae-Young Kim ◽

Chang-Yeol Yeon ◽

Chang-Hyeon An ◽

...

Keyword(s):

Gene Expression ◽

Expression Pattern ◽

Ex Vivo ◽

Developmental Regulation ◽

Expression Patterns ◽

Tooth Germ ◽

Culture Method ◽

Tooth Pulp ◽

Altered Expression ◽

Tooth Morphogenesis

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that post-transcriptionally regulate gene expression in organisms. Most mammalian miRNAs influence biological processes, including developmental changes, tissue morphogenesis and the maintenance of tissue identity, cell growth, differentiation, apoptosis, and metabolism. The miR-206-3p has been correlated with cancer; however, developmental roles of this miRNA are unclear. In this study, we examined the expression pattern and evaluated the developmental regulation of miR-206-3p during tooth morphogenesis using ex-vivo culture method. The expression pattern of miR-206-3p was examined in the epithelium and mesenchyme of developing tooth germ with stage-specific manners. Perturbation of the expression of miR-206-3p clearly altered expression patterns of dental-development–related signaling molecules, including Axin2, Bmp2, Fgf4, Lef1 and Shh. The gene expression complemented with change in cellular events including, apoptosis and proliferation which caused altered crown and pulp morphogenesis in renal-capsule–calcified teeth. Especially, mislocalization of β-Catenin and SMAD1/5/8 were observed alongside dramatic alterations in the expression patterns of Fgf4 and Shh. Overall, our data suggest that the miR-206-3p regulate the cellular physiology during tooth morphogenesis through modulation of the Wnt, Bmp, Fgf, and Shh signaling pathways to form proper tooth pulp and crown.

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Regulation of Stress Granule Formation by Inflammation, Vascular Injury, and Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.313034 ◽

2019 ◽

Vol 39 (10) ◽

pp. 2014-2027 ◽

Cited By ~ 7

Author(s):

Allison B. Herman ◽

Milessa Silva Afonso ◽

Sheri E. Kelemen ◽

Mitali Ray ◽

Christine N. Vrakas ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Rna Binding ◽

Binding Protein ◽

Muscle Cells ◽

Stress Granule ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Granule Formation ◽

Altered Expression

Objective: Stress granules (SGs) are dynamic cytoplasmic aggregates containing mRNA, RNA-binding proteins, and translation factors that form in response to cellular stress. SGs have been shown to contribute to the pathogenesis of several human diseases, but their role in vascular diseases is unknown. This study shows that SGs accumulate in vascular smooth muscle cells (VSMCs) and macrophages during atherosclerosis. Approach and Results: Immunohistochemical analysis of atherosclerotic plaques from LDLR − /− mice revealed an increase in the stress granule-specific markers Ras-G3BP1 (GTPase-activating protein SH3 domain-binding protein) and PABP (poly-A-binding protein) in intimal macrophages and smooth muscle cells that correlated with disease progression. In vitro, PABP+ and G3BP1+ SGs were rapidly induced in VSMC and bone marrow–derived macrophages in response to atherosclerotic stimuli, including oxidized low-density lipoprotein and mediators of mitochondrial or oxidative stress. We observed an increase in eIF2α (eukaryotic translation initiation factor 2-alpha) phosphorylation, a requisite for stress granule formation, in cells exposed to these stimuli. Interestingly, SG formation, PABP expression, and eIF2α phosphorylation in VSMCs is reversed by treatment with the anti-inflammatory cytokine interleukin-19. Microtubule inhibitors reduced stress granule accumulation in VSMC, suggesting cytoskeletal regulation of stress granule formation. SG formation in VSMCs was also observed in other vascular disease pathologies, including vascular restenosis. Reduction of SG component G3BP1 by siRNA significantly altered expression profiles of inflammatory, apoptotic, and proliferative genes. Conclusions: These results indicate that SG formation is a common feature of the vascular response to injury and disease, and that modification of inflammation reduces stress granule formation in VSMC.

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RNA-binding protein altered expression and mislocalization in multiple sclerosis

10.1101/829457 ◽

2019 ◽

Author(s):

Katsuhisa Masaki ◽

Yoshifumi Sonobe ◽

Ghanashyam Ghadge ◽

Peter Pytel ◽

Paula Lépine ◽

...

Keyword(s):

Multiple Sclerosis ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Metabolic Stress ◽

Nucleocytoplasmic Transport ◽

Altered Expression ◽

Polypyrimidine Tract Binding Protein ◽

Demyelinating Lesions

AbstractObjectiveNuclear depletion and mislocalization of RNA-binding proteins (RBPs) trans-activation response DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS) are thought to contribute to the pathogenesis of a number of disorders, including amyotrophic lateral sclerosis (ALS). We recently found that TDP-43 as well as polypyrimidine tract binding protein (PTB) have decreased expression and mislocalization in oligodendrocytes in demyelinated lesions in an experimental mouse model of multiple sclerosis (MS) caused by Theiler’s murine encephalomyelitis virus infection.MethodsThe latter finding prompted us to investigate TDP-43, FUS, and PTB in the demyelinated lesions of MS and in in vitro cultured human brain-derived oligodendrocytes.ResultsWe found: i) mislocalized TDP-43 in oligodendrocytes in active lesions in some MS patients; ii) decreased PTB1 expression in oligodendrocytes in mixed active/inactive demyelinating lesions; iii) decreased nuclear expression of PTB2 in neurons in cortical demyelinating lesions; iv) nuclear depletion of TDP-43 in oligodendrocytes under metabolic stress induced by low glucose/low nutrient conditions compared to optimal culture conditions.ConclusionTDP-43 has been found to have a key role in oligodendrocyte function and viability, while PTB is important in neuronal differentiation, suggesting that altered expression and mislocalization of these RBPs in MS lesions may contribute to the pathogenesis of demyelination and neurodegeneration. Our findings also identify nucleocytoplasmic transport as a target for treatment.

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EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer

Cancer Cell International ◽

10.1186/s12935-020-01622-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Dongbo Wu ◽

Fanglan Wu ◽

Birong Li ◽

Wei Huang ◽

Donglian Wang

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Expression Pattern ◽

Transforming Growth Factor Beta ◽

Promoter Methylation ◽

Transforming Growth Factor ◽

Expression Patterns ◽

Luciferase Reporter ◽

Altered Expression ◽

Gene Assay

Abstract Background It has been known that ovarian cancer (OC) is a leading cause for women mortality globally. We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis. Methods High expression patterns of EZH2 and miR-139 and low LPA1 expression pattern in OC were evaluated using RT-qPCR and immunoblotting, while their correlation was assessed by the Spearman’s rank and Pearson’s correlation coefficient. Subsequently, dual-luciferase reporter gene assay was applied to validate the binding relationship between miR-139 and LPA1, while H3K27me enrichment was assessed by ChIP assay. After that, the effects of altered expression of EZH2, miR-194, or LPA1 on the cell biological functions and the expression pattern of TGF-related factors were evaluated. Results We found that EZH2 repressed the miR-139 expression pattern by recruiting H3K27me3 to promote miR-139 promoter methylation, while silencing of EZH2 suppressed in vitro cancer progression by increasing miR-139. LPA1 was a target of miR-139, and could activate the TGF-β signaling pathway, which hastened the OC progression. miR-139-targeted inhibition of LPA1 and LPA1-activated TGF-β signaling pathway were evidenced to be critical mechanisms underlying the effects of EZH2 on OC cells. Lastly, silencing of EZH2 inhibited the xenograft growth in vivo. Conclusions EZH2 could down-regulate miR-139 expression pattern by recruiting H3K27me3 to promote the miR-139 promoter methylation and activate the TGF-β pathway by up-regulating LPA1, which contributed to the progression of OC. The current study may possess potentials for OC treatment.

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Expression Pattern of Major Poly C Binding Protein (Pcbp) Isoforms in Cancer Cell Lines of Cervix, Melanoma and Muscle

Biosciences Biotechnology Research Asia ◽

10.13005/bbra/2768 ◽

2019 ◽

Vol 16 (3) ◽

pp. 537-543

Author(s):

Gargi Ghosh ◽

Utpal Basu

Keyword(s):

Expression Pattern ◽

Cell Lines ◽

Cancer Cell ◽

Rna Binding ◽

Rna Virus ◽

Binding Protein ◽

Cancer Cell Lines ◽

Cellular Functions ◽

Kh Domain ◽

Post Transcriptional Regulation

Poly (C) binding proteins (PCBPs) are members of sequence specific RNA binding protein family with conserved KH domain. There are four identified isoforms such as Pcbp1 or α-CP1 (α-Complex proteins), Pcbp2 or α-CP2, Pcbp3 or α-CP3 and Pcbp4 or α-CP4. Among them Pcbp1 and Pcbp2 are the most studied and found to be associated with various cellular functions such as transcriptional regulations, translational regulations and mRNA stability. Although two proteins share extensive similarity, they differ in function and localization. Pcbp1 has role in tumorigenesis, and metastasis, which are key phenomena of cancer. Role of pcbp2 has been well documented in the biology of RNA virus, namely translation and replication. Here, we studied expression pattern of Pcbp1 and Pcbp2 in three different cancer cell lines namely HeLa, RD, and A375 originated from different tissues. The results indicate not only differential abundance of these two proteins in three cell lines, but also discordant expression of pcbp1 in mRNA and protein level in three cell lines. The study therefore suggests post-transcriptional regulation of pcbp1 expression in these cell lines.

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The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03965-w ◽

2021 ◽

Author(s):

Shekoufeh Almasi ◽

Bernard J. Jasmin

Keyword(s):

Rna Binding ◽

Current Knowledge ◽

Binding Protein ◽

Neuromuscular Disorders ◽

Expression Patterns ◽

Rna Binding Protein ◽

Rna Metabolism ◽

Cancer Development ◽

Cell Functions

AbstractThe double-stranded multifunctional RNA-binding protein (dsRBP) Staufen was initially discovered in insects as a regulator of mRNA localization. Later, its mammalian orthologs have been described in different organisms, including humans. Two human orthologues of Staufen, named Staufen1 (STAU1) and Staufen2 (STAU2), share some structural and functional similarities. However, given their different spatio-temporal expression patterns, each of these orthologues plays distinct roles in cells. In the current review, we focus on the role of STAU1 in cell functions and cancer development. Since its discovery, STAU1 has mostly been studied for its involvement in various aspects of RNA metabolism. Given the pivotal role of RNA metabolism within cells, recent studies have explored the mechanistic impact of STAU1 in a wide variety of cell functions ranging from cell growth to cell death, as well as in various disease states. In particular, there has been increasing attention on the role of STAU1 in neuromuscular disorders, neurodegeneration, and cancer. Here, we provide an overview of the current knowledge on the role of STAU1 in RNA metabolism and cell functions. We also highlight the link between STAU1-mediated control of cellular functions and cancer development, progression, and treatment. Hence, our review emphasizes the potential of STAU1 as a novel biomarker and therapeutic target for cancer diagnosis and treatment, respectively.

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Two parallel arms of the heterochronic pathway direct coordinated juvenile-to-adult transition through distinct LIN-29 isoforms

10.1101/783001 ◽

2019 ◽

Author(s):

Chiara Azzi ◽

Florian Aeschimann ◽

Anca Neagu ◽

Helge Großhans

Keyword(s):

Transcription Factor ◽

Rna Binding ◽

Binding Protein ◽

Expression Patterns ◽

Rna Binding Protein ◽

Adult Transition ◽

Physiological Processes ◽

Regulatory Cascade ◽

The Individual ◽

Organismal Development

AbstractRobust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, the timely transition from juvenile to adult is controlled by the heterochronic pathway, a regulatory cascade of conserved proteins and small RNAs. The heterochronic pathway culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of juvenile-to-adult (J/A) transition events. Here, we reveal that two LIN-29 isoforms fulfill distinct functions during the J/A transition. We show that the functional differences between the isoforms do not stem from differences in their sequences, but from their distinct spatiotemporal expression, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique lin-29 isoform expression patterns are generated by the RNA-binding protein LIN-41 for lin-29a, and the transcription factor HBL-1 for lin-29b. By regulating both HBL-1 and LIN-41, the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity. Thus, our findings reveal that a coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.

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