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 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

LncRNA RP3-326I13.1 Promoted Cisplatin Resistance of Lung Adenocarcinoma by Collaborating RNA Binding Protein HSP90B and Upregulating Downstream Molecule MMP13 

2020 ◽  
Author(s):  
Huixin Zhou ◽  
Shihao Xu ◽  
Wenjing Shi ◽  
Xiaolu Huang ◽  
Jie Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Nude Mice ◽  
Rna Binding ◽  
Cisplatin Resistance ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
A549 Cells ◽  
Downstream Target

Abstract Background:We previously obtained a lncRNA RP3-326I13.1, which significantly upregulated by cisplatin resistance in lung adenocarcinoma (LAD), but the biological function and molecular mechanism is unclear. Methods:Expression levels of RP3-326I13.1 and HSP90B mRNA were estimated by qPCR from 57 pairs of LAD and NT samples without and with cisplatin. Knockdown and overexpression in A549/DDP and A549 cell lines by lentiviral- mediated techniques to observe changes in tumor behavior in A549/DDP and A549 cells, as well as tumorigenicity in experimental nude mice. The ranscriptome was sequenced to obtain downstream target molecules of RP3-326I13.1 and RNA-binding proteins were obtained using RNA pulldown. Results: QPCR showed that the expression level of RP3-326I13.1 and HSP90B mRNA in A549/DDP cells, LAD tissues and progressive LAD tissues (cisplatin treatment was not effective) were tangibly higher than that of A549 cells, adjacent tissues, and complete remission (P=0.0037, P=0.0181; P=0.0027, P=0.009 and P=0.002, P=0.007). RP3-326I13.1 markedly enhanced the proliferation, migrate, invasion, clonal proliferation ability of LAD cell lines and speed and weight of tumorigenicity in nude mice experiment while increased the proportion of G1 phase cells (P=0.019). RNA-pull down and mass spectrometry obtained RNA binding protein HSP90B and HSP90B clearly decreased proliferation, invasive ability while increased the apoptosis of LAD cell lines after knocked down. We found matrix metalloproteinase-13 (MMP-13) was RP3-326I13.1 downstream target gene. Conclusions: So, RP3-326I13.1 was a drug-resistant relative lncRNA promoted cisplatin resistance of lung adenocarcinoma by collaborating RNA binding protein HSP90B and upregulating downstream target molecule MMP13.

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

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 Development and validation of a prediction model for lung adenocarcinoma based on RNA-binding protein

2021 ◽  
Vol 9 (6) ◽  
pp. 474-474
Author(s):  
Longjun Yang ◽  
◽  
Rusi Zhang ◽  
Guangran Guo ◽  
Gongming Wang ◽  
...  
Keyword(s):  
Prediction Model ◽  
Lung Adenocarcinoma ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Development And Validation

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.

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