scholarly journals Identification and validation of RNA binding protein-associated prognostic model for Neuroblastoma

2021 ◽  
Author(s):  
Jun Yang ◽  
Jiaying Zhou ◽  
Cuili Li ◽  
Shaohua Wang
Keyword(s):  
Survival Rate ◽  
Prognostic Model ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Characteristic Curve ◽  
Rna Binding Protein ◽  
Validation Data ◽  
Data Set ◽  
Significant Difference

Abstract ABSTRACT Background: The abnormal expression of RNA binding protein (RBP) may be related to the development and progress of cancer. However, little is known about the mechanism of RBP in neuroblastoma (NB). Methods: We downloaded the RNA expression data of NB and normal nervous tissues from the (TARGET) database and GTEx database, and determined the differential expression of RBP between normal and cancerous tissues. Then the function and prognostic value of these RBPs were systematically studied. Results: A total of 348 differentially expressed RBPs were identified, together with 166 up-regulated RBPs and 182 down-regulated RBPs. Two hub RBPs (CPEB3 and CTU1) were identified as prognostic-related genes and chose to build prognostic risk score models. Further analysis showed that based on this model, the overall survival rate of patients in the high-risk subgroup was lower (P=2.152e-04). The area under the curve(AUC) of the receiver-operator characteristic curve(ROC) of the prognostic model is 0.720 in the TARGET cohort. There is a significant difference in the survival rate of patients in the high and low risk subgroups in the validation data set GSE85047 (P = 0.1237e-08), the AUC is 0.730. Conclusions: RNA binding protein (CPEB3 and CTU1) can be used as molecular markers of NB. Keywords: Neuroblastoma, RNA binding proteins, prognostic, TARGET, GTEx

scholarly journals Identification and Validation of RNA Binding Protein-associated Prognostic Model for Neuroblastoma

2020 ◽  
Author(s):  
JUN YANG ◽  
Jiaying Zhou ◽  
Cuili Li ◽  
Shaohua Wang
Keyword(s):  
Survival Rate ◽  
Prognostic Model ◽  
Rna Binding ◽  
Binding Protein ◽  
Characteristic Curve ◽  
Rna Binding Protein ◽  
Receiver Operator Characteristic Curve ◽  
Validation Data ◽  
Data Set ◽  
Significant Difference

Abstract Background: The abnormal expression of RNA binding protein (RBP) may be related to the development and progress of cancer. However, little is known about the mechanism of RBP in neuroblastoma (NB). Methods: We downloaded the RNA expression data of NB and normal nervous tissues from the (TARGET) database and GTEx database, and determined the differential expression of RBP between normal and cancerous tissues. Then the function and prognostic value of these RBPs were systematically studied. Results: A total of 348 differentially expressed RBPs were identified, together with 166 up-regulated RBPs and 182 down-regulated RBPs. Two hub RBPs (CPEB3 and CTU1) were identified as prognostic-related genes and chose to build prognostic risk score models. Further analysis showed that based on this model, the overall survival rate of patients in the high-risk subgroup was lower (P=2.152e-04). The area under the curve(AUC) of the receiver-operator characteristic curve(ROC) of the prognostic model is 0.720 in the TARGET cohort. There is a significant difference in the survival rate of patients in the high and low risk subgroups in the validation data set GSE85047 (P = 0.1237e-08), the AUC is 0.730. Conclusions: RNA binding protein (CPEB3 and CTU1) can be used as molecular markers of NB.

scholarly journals Development and Validation of a Novel Five-Gene-Based RNA Binding Protein Associated Prognostic Model for Human Colon Cancer

2020 ◽  
Author(s):  
Haoling Liu ◽  
Qingquan Bai ◽  
Zhaoyang Lu ◽  
Xuan Song ◽  
Yao Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Model ◽  
Rna Binding ◽  
Malignant Tumors ◽  
Binding Protein ◽  
Characteristic Curve ◽  
Rna Binding Protein ◽  
The Cancer Genome Atlas ◽  
Human Colon Cancer ◽  
Good Ability

Abstract Background: Dysregulation of RNA binding protein (RBP) expression has been reported in various malignant tumors, and it is related to the occurrence and development of cancer. However, the role of RBPs in colon cancer remains unclear. Methods: We downloaded the RNA sequencing data of colon cancer from The Cancer Genome Atlas (TCGA) database, and determined the differently expressed RBPs between normal and cancer tissues. Then, through a series of bioinformatics analysis, we systematically studied the expression and prognostic value of these RBPs.Result: A total of 490 different expression differently expressed RBPs were identified, including 323 up-regulated and 167 down regulated RBPs. Five RBPs (PNLDC1, NSUN6, NOL3, PPARGC1A, LRRFIP2) were identified as prognosis related genes for the construction of prognostic model. Further analysis showed that the overall survival rate (OS) of patients in the high-risk subgroup was worse than that in the low-risk subgroup based on this model. The area under the characteristic curve of time-dependent receiver was 0.691 in TCGA and 0.624 in GEO, which confirmed the prognostic model to be a good one. We also established a nominal map based on the internal validation in 5 RBPs mRNAs and TCGA sequeues, showing a good ability to differentiate colon cancer.Conclusions: We screened RBPs expression differences between colon cancer and adjacent non tumor colon tissues using the TCGA database to identify potential gene biomarkers.Besides,a very effective prediction model was constructed and tested based on the differential expression of RBPs using the TCGA and Gene Expression Omnibus (GEO) database.We also Validated of the relationship between the expression of five RBPs and prognosis

scholarly journals Predicting the Clinical Outcome of Lung Adenocarcinoma Using a Novel Gene Pair Signature Related to RNA-Binding Protein

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Liangliang Meng ◽  
Xiaoxi He ◽  
Xiao Zhang ◽  
Xiaobo Zhang ◽  
Yingtian Wei ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Adenocarcinoma ◽  
Gene Pair ◽  
Prognostic Model ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Risk Group ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
High Risk Group

Adenocarcinoma is the most common type of lung cancer, and patients have varying prognoses. RNA-binding proteins (RBP) are deemed to be closely associated with tumorigenesis and development, but the exact mechanism is currently unknown. This study was aimed at constructing a new robust prognostic model based on RNA-binding protein-related gene pair scores for better clinical guidance. The model for this study was constructed based on data of lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. Prognosis-related RBP gene pair models were created based on differentially expressed genes, and the accuracy of the models was verified in a different age, staging, and other subdatasets. A total of 379 RNA-binding protein-related genes were differentially expressed in tumor tissue. From these genes, we constructed a prognostic model consisting of 33 gene pairs, which were found to be significantly associated with survival in TCGA dataset ( P < 0.0001 , hazard ratio   HR = 4.380 (3.139 to 6.111)) and different subdatasets. As expected, the results were verified in the GEO validation cohort ( P = 7.8 × 10 − 3 , HR = 1.597 (1.095 to 2.325)). We found that the signature exhibited an independent prognostic factor in both the univariate and multivariate Cox regression analyses ( P < 0.001 ). CIBERSORT was applied to estimate the fractions of infiltrated immune cells in bulk tumor tissues. CD8 T cells, activated dendritic cells, regulatory T cells (Tregs), and activated CD4 memory T cells presented a significantly lower fraction in the high-risk group ( P < 0.01 ). Patients in the high-risk group had significantly higher tumor mutational burden (TMB) ( P = 4.953 e − 04 ) and lower levels of immune cells ( P = 3.473 e − 05 ) and stromal cells ( P = 0.005 ) in the tumor microenvironment than those in the low-risk group. Furthermore, the Protein-protein interaction (PPI) network and various enrichment analyses have genuinely uncovered the interrelationships and potential functions of the RBP genes within the model. The results of the present study validated the importance of RNA-binding proteins in tumorigenesis and progression and support the RBP gene-related signature as a promising marker for prognosis prediction in lung adenocarcinoma.

scholarly journals Development and validation of a novel five-gene-based RNA binding protein associated prognostic model for human colon cancer

2020 ◽  
Author(s):  
Haoling Liu ◽  
Qingquan Bai ◽  
Zhaoyang Lu ◽  
Xuan Song ◽  
Ye Jin ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Model ◽  
Rna Binding ◽  
Malignant Tumors ◽  
Binding Protein ◽  
Characteristic Curve ◽  
Rna Binding Protein ◽  
The Cancer Genome Atlas ◽  
Human Colon Cancer ◽  
Good Ability

Abstract BackgroundDysregulation of RNA binding protein (RBP) expression has been reported in various malignant tumors, and it is related to the occurrence and development of cancer. However, the role of RBPs in colon cancer remains unclear.MethodsWe downloaded the RNA sequencing data of colon cancer from The Cancer Genome Atlas (TCGA) database, and determined the differently expressed RBPs between normal and cancer tissues. Then, through a series of bioinformatics analysis, we systematically studied the expression and prognostic value of these RBPs.ResultA total of 490 different expression differently expressed RBPs were identified, including 323 up-regulated and 167 down. regulated RBPs. Five RBPs (PNLDC1, NSUN6, NOL3, PPARGC1A, LRRFIP2) were identified as prognosis related genes for the construction of prognostic model. Further analysis showed that the overall survival rate (OS) of patients in the high-risk subgroup was worse than that in the low-risk subgroup based on this model. The area under the characteristic curve of time-dependent receiver was 0.691 in TCGA and 0.624 in GEO, which confirmed the prognostic model to be a good one. We also established a nominal map based on the internal validation in 5 RBPs mRNAs and TCGA sequeues, showing a good ability to differentiate colon cancer.ConclusionsWe screened RBPs expression differences between colon cancer and adjacent non tumor colon tissues using the TCGA database to identify potential gene biomarkers.Besides,a very effective prediction model was constructed and tested based on the differential expression of RBPs using the TCGA and Gene Expression Omnibus (GEO) database.We also Validated of the relationship between the expression of five RBPs and prognosis

scholarly journals The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 552
Author(s):  
Jasmine Harley ◽  
Benjamin E. Clarke ◽  
Rickie Patani
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mitochondrial Dysfunction ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Therapeutic Strategies ◽  
Lateral Sclerosis

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.

scholarly journals The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages

2011 ◽  
Vol 22 (16) ◽  
pp. 2875-2885 ◽  
Author(s):  
Mai Nguyen Chi ◽  
Jacques Auriol ◽  
Bernard Jégou ◽  
Dimitris L. Kontoyiannis ◽  
James M.A. Turner ◽  
...  
Keyword(s):  
Germ Cells ◽  
Posttranscriptional Regulation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Female Sterility ◽  
Targeted Deletion

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.

scholarly journals Investigating the Roles of RNA Binding Protein Combinations in Neuronal Function and Organismal Behavior

2019 ◽  
Vol 4 (Spring 2019) ◽  
Author(s):  
Alexa Vandenburg
Keyword(s):  
Binding Sites ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type ◽  
C Elegans ◽  
Neuronal Gene ◽  
Touch Response

The Norris lab recently identified two RNA binding proteins required for proper neuron-specific splicing. The lab conducted touch- response behavioral assays to assess the function of these proteins in touch-sensing neurons. After isolating C. elegans worms with specific phenotypes, the lab used automated computer tracking and video analysis to record the worms’ behavior. The behavior of mutant worms differed from that of wild-type worms. The Norris lab also discovered two possible RNA binding protein sites in SAD-1, a neuronal gene implicated in the neuronal development of C. elegans1. These two binding sites may control the splicing of SAD-1. The lab transferred mutated DNA into the genome of wild-type worms by injecting a mutated plasmid. The newly transformed worms fluoresced green, indicating that the two binding sites control SAD-1 splicing.

PUB1 is a major nuclear and cytoplasmic polyadenylated RNA-binding protein in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (10) ◽  
pp. 6102-6113
Author(s):  
J T Anderson ◽  
M R Paddy ◽  
M S Swanson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Uv Light ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Rna Binding Protein ◽  
Polyadenylated Rna ◽  
Polyadenylated Rnas

Proteins that directly associate with nuclear polyadenylated RNAs, or heterogeneous nuclear RNA-binding proteins (hnRNPs), and those that associate with cytoplasmic mRNAs, or mRNA-binding proteins (mRNPs), play important roles in regulating gene expression at the posttranscriptional level. Previous work with a variety of eukaryotic cells has demonstrated that hnRNPs are localized predominantly within the nucleus whereas mRNPs are cytoplasmic. While studying proteins associated with polyadenylated RNAs in Saccharomyces cerevisiae, we discovered an abundant polyuridylate-binding protein, PUB1, which appears to be both an hnRNP and an mRNP. PUB1 and PAB1, the polyadenylate tail-binding protein, are the two major proteins cross-linked by UV light to polyadenylated RNAs in vivo. The deduced primary structure of PUB1 indicates that it is a member of the ribonucleoprotein consensus sequence family of RNA-binding proteins and is structurally related to the human hnRNP M proteins. Even though the PUB1 protein is a major cellular polyadenylated RNA-binding protein, it is nonessential for cell growth. Indirect cellular immunofluorescence combined with digital image processing allowed a detailed comparison of the intracellular distributions of PUB1 and PAB1. While PAB1 is predominantly, and relatively uniformly, distributed within the cytoplasm, PUB1 is localized in a nonuniform pattern throughout both the nucleus and the cytoplasm. The cytoplasmic distribution of PUB1 is considerably more discontinuous than that of PAB1. Furthermore, sucrose gradient sedimentation analysis demonstrates that PAB1 cofractionates with polyribosomes whereas PUB1 does not. These results suggest that PUB1 is both an hnRNP and an mRNP and that it may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm.

scholarly journals A potential role for a novel ZC3H5 complex in regulating mRNA translation in Trypanosoma brucei

2020 ◽  
Vol 295 (42) ◽  
pp. 14291-14304
Author(s):  
Kathrin Bajak ◽  
Kevin Leiss ◽  
Christine Clayton ◽  
Esteban Erben
Keyword(s):  
Gene Expression ◽  
Trypanosoma Brucei ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Affinity Purification ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Mrna Translation

In Trypanosoma brucei and related kinetoplastids, gene expression regulation occurs mostly posttranscriptionally. Consequently, RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Yet, the roles of many RNA-binding proteins are not understood. Our previous research identified the RNA-binding protein ZC3H5 as possibly involved in gene repression, but its role in controlling gene expression was unknown. We here show that ZC3H5 is an essential cytoplasmic RNA-binding protein. RNAi targeting ZC3H5 causes accumulation of precytokinetic cells followed by rapid cell death. Affinity purification and pairwise yeast two-hybrid analysis suggest that ZC3H5 forms a complex with three other proteins, encoded by genes Tb927.11.4900, Tb927.8.1500, and Tb927.7.3040. RNA immunoprecipitation revealed that ZC3H5 is preferentially associated with poorly translated, low-stability mRNAs, the 5′-untranslated regions and coding regions of which are enriched in the motif (U/A)UAG(U/A). As previously found in high-throughput analyses, artificial tethering of ZC3H5 to a reporter mRNA or other complex components repressed reporter expression. However, depletion of ZC3H5 in vivo caused only very minor decreases in a few targets, marked increases in the abundances of very stable mRNAs, an increase in monosomes at the expense of large polysomes, and appearance of “halfmer” disomes containing two 80S subunits and one 40S subunit. We speculate that the ZC3H5 complex might be implicated in quality control during the translation of suboptimal open reading frames.

scholarly journals The Potential Contribution of Dysfunctional RNA-Binding Proteins to the Pathogenesis of Neurodegeneration in Multiple Sclerosis and Relevant Models

2020 ◽  
Vol 21 (13) ◽  
pp. 4571 ◽  
Author(s):  
Cole D. Libner ◽  
Hannah E. Salapa ◽  
Michael C. Levin
Keyword(s):  
Multiple Sclerosis ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Potential Contribution ◽  
Novel Therapies ◽  
Permanent Disability ◽  
Central Nervous System Damage ◽  
Protein Dysfunction

Neurodegeneration in multiple sclerosis (MS) is believed to underlie disease progression and permanent disability. Many mechanisms of neurodegeneration in MS have been proposed, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, and RNA-binding protein dysfunction. The purpose of this review is to highlight mechanisms of neurodegeneration in MS and its models, with a focus on RNA-binding protein dysfunction. Studying RNA-binding protein dysfunction addresses a gap in our understanding of the pathogenesis of MS, which will allow for novel therapies to be generated to attenuate neurodegeneration before irreversible central nervous system damage occurs.

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