RNA-Binding Proteins in Acute Leukemias

Schuschel, Konstantin; Helwig, Matthias; Hüttelmaier, Stefan; Heckl, Dirk; Klusmann, Jan‐Henning; Hoell, Jessica I.

doi:10.3390/ijms21103409

Cited by 39 publications

(37 citation statements)

References 252 publications

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“…However, it mostly behaves as a tumor suppressor in acute leukemia [12]. RBPs constitute a key factor of the post-transcriptional process and play an important role in the regulation of RNA in gastrointestinal [13] and colorectal cancers [14].…”

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confidence: 99%

Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

Guo

Shao

Jiang

et al. 2020

Preprint

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Background Alterations in RNA-binding proteins (RBPs) are reported in various cancer types; however, the role of RBPs in bladder urothelial cancer (BLCA) remains unknown. This study aimed to systematically examine the function and prognostic significance of RBPs in bladder cancer using bioinformatics analyses. Methods RNA sequencing and clinical data for BLCA were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed RBPs (DERBPs) between normal and cancer tissues were identified. Protein-protein interaction (PPI) network of DERBPs was established, and enrichment analysis and visualizations were performed. A total of 404 patients with BLCA from TCGA database were randomly divided into training and testing groups. A prognostic model was constructed using the data from training group, and validated in the testing group. Receiver operating characteristic (ROC) curve and survival analysis were performed to explore the prognostic value of the model. A nomogram was established to predict survival in bladder cancer patients. Finally, the verification of prognosis-related hub RBP survival analysis were performed. Results A total of 388 DERBPs were identified, including 219 upregulated and 169 downregulated RBPs. All RBPs were screened for prognostic model establishment and 9 RBPs (TRIM71, YTHDC1, DARS2, XPOT, ZNF106, FTO, IPO7, EFTUD2, and CTU1) were regarded as prognosis-related hub RBPs in BLCA. Further analysis revealed worse overall survival (OS) in the high-risk cohort compared to the model-based low-risk cohort. The area under the ROC curve was 0.752 in the training group and 0.701 in the testing group, which confirms the good prediction ability. A nomogram was established according to nine prognosis-related RBPs, which showed well predicting ability for BLCA. BLCA patients with high DARS2, XPOT, ZNF106, FTO, and IPO7 expression (on the contrary, low YTHDC1 and CTU1 expression) were correlated to poor overall survival. Conclusions The prognosis-related hub RBPs may be involved in oncogenesis, development, and metastasis of BLCA. Our results will be of great significance in revealing the pathogenesis of BLCA, and developing new therapeutic targets and prognostic molecular markers.

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confidence: 99%

Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

Guo

Shao

Jiang

et al. 2020

Preprint

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“…The fate of mature mRNA is affected by non-coding RNAs and RNA-binding proteins (RBPs). RBPs, such as transcription factor, is a crucial regulator for post-transcriptional regulation, and the regulation of the RBPs is highly dependent on the binding sequences [24]. Information on the studied SNPs assessed in Hap-loReg and Regulome DB datasets showed that rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 were all overlap in regions with promoter or enhancer function in tissues such as the brain.…”

Section: Discussionmentioning

confidence: 99%

Functional polymorphisms and transcriptional analysis in the 5′ region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

et al. 2020

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Background The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5′ regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. Methods Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5′ regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. Results Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from − 1587 to − 1371 bp (TSS, + 1), − 1149 to − 894 bp, − 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions − 603 to − 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. Conclusions HTR1B 5′ regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions − 1587 to − 1371 bp, − 1149 to − 894 bp, − 603 to − 316 bp, − 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

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“…The fate of mature mRNA is affected by non-coding RNAs and RNA-binding proteins (RBPs). RBPs, such as transcription factor, is a crucial regulator for post-transcriptional regulation, and the regulation of the RBPs is highly dependent on the binding sequences [24]. Information on the studied SNPs assessed in HaploReg and Regulome DB datasets showed that rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 were all overlap in regions with promoter or enhancer function in tissues such as the brain.…”

Section: Discussionmentioning

confidence: 99%

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

Xia

Ding

Xuan

et al. 2020

Preprint

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Background The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders.MethodsSix haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system.Results Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from -1587 to -1371 bp (TSS, +1), -1149 to -894 bp, -39 to +130 bp, +130 to +341 bp, and +341 to +505 bp upregulated gene expression. In contrast, regions -603 to -316 bp and +130 to +341 bp downregulated gene expression. Region +341 to +505 bp played a decisive role in gene transcription.Conclusions HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region +341~+505 bp. Regions -1587 to -1371 bp, -1149 to -894 bp, -603 to -316 bp, -39 to +130 bp, and +130 to +341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

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RNA-Binding Proteins in Acute Leukemias

Cited by 39 publications

References 252 publications

Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

Functional polymorphisms and transcriptional analysis in the 5′ region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders

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