Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

Masuda, Kiyoshi; Kuwano, Yuki

doi:10.1002/wrna.1520

Cited by 72 publications

(71 citation statements)

References 231 publications

(363 reference statements)

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“…RNA binding proteins (RBPs) are proteins that interact with various types of RNA and are ubiquitously expressed in cells (Masuda and Kuwano, 2019;New et al, 2019;Otsuka et al, 2019). A total of 1542 RBPs have been identified by highthroughput screening in human cells, representing 7.5% of all protein coding genes (Gerstberger et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…A total of 1542 RBPs have been identified by highthroughput screening in human cells, representing 7.5% of all protein coding genes (Gerstberger et al, 2014). These RBPs affect post-transcriptional events in cells and modulate cell physiology, and are therefore involved in multiple biological processes including RNA splicing, mRNA stability, export to the cytoplasm, localization, and protein translation (Masuda and Kuwano, 2019;Nahalka, 2019). Given that RPBs perform various critical functions in post-transcriptional events, it is unsurprising that alterations in RBPs are closely related to the initiation and progression of many human diseases.…”

Section: Introductionmentioning

confidence: 99%

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Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Xue

Gao

et al. 2020

Front. Genet.

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Lung cancer is the leading cause of cancer-related deaths worldwide. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. However, the functions of RBPs in lung squamous cell carcinoma (LUSC) remain unclear. In this study, we obtained gene expression data and corresponding clinical information for LUSC from The Cancer Genome Atlas (TCGA) database, identified aberrantly expressed RBPs between tumors and normal tissue, and conducted a series of bioinformatics analyses to explore the expression and prognostic value of these RBPs. A total of 300 aberrantly expressed RBPs were obtained, comprising 59 downregulated and 241 upregulated RBPs. Functional enrichment analysis indicated that the differentially expressed RBPs were mainly associated with mRNA metabolic processes, RNA processing, RNA modification, regulation of translation, the TGF-beta signaling pathway, and the Toll-like receptor signaling pathway. Nine RBP genes (A1CF, EIF2B5, LSM1, LSM7, MBNL2, RSRC1, TRMU, TTF2, and ZCCHC5) were identified as prognosis-associated hub genes by univariate, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier survival, and multivariate Cox regression analyses, and were used to construct the prognostic model. Further analysis demonstrated that high risk scores for patients were significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.712 at 3 years and 0.696 at 5 years. We also developed a nomogram based on nine RBP genes, with internal validation in the TCGA cohort, which showed a favorable predictive efficacy for prognosis in LUSC. Our results provide novel insights into the pathogenesis of LUSC. The nine-RBP gene signature showed predictive value for LUSC prognosis, with potential applications in clinical decision-making and individualized treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Xue

Gao

et al. 2020

Front. Genet.

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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]. Despite the emergence of RBPs as key regulators of every cancer hallmark, very little is known about their potential mechanisms and downstream carcinogenic targets, particularly with regard to bladder cancer.…”

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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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“…Liver cancer is influenced by post-transcriptional mechanisms that dynamically regulate protein expression. (Wong et al 2018;Goldstrohm et al 2018) Cis-regulatory RNA elements and trans-acting factors (Gerstberger et al 2014;Moore 2005) including RNA-binding proteins (RBPs) play an essential role in gene expression in cancer cells (Masuda & Kuwano 2019). Recently, a group of RBPS termed MEX-3 RNA binding family member (MEX3) was identified in the nematode Caenorhabditis elegans (Ciosk et al 2006) and revealed one of the few RBPs with carcinogenic or tumor suppressor activity (Kim et al 2009;Pereira et al 2013a).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #3 of "Clinical characteristics and prognostic value of MEX3A mRNA in liver cancer (v0.2)"

2020

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Background. MEX3A is an RNA-binding proteins (RBPs) that promotes the proliferation, invasion, migration and viability of cancer cells. The aim of this study was to explore the clinicopathological characteristics and prognostic significance of MEX3A mRNA expression in liver cancer. Methods. RNA-Seq and clinical data were collected from The Cancer Genome Atlas (TCGA). Boxplots were used to represent discrete variables of MEX3A. Chisquare tests were used to analyze the correlation between clinical features and MEX3A expression. Receiver operating characteristic (ROC) curves were used to confirm diagnostic ability. Independent prognostic ability and values were assessed using Kaplan-Meier curves and Cox analysis. Results. We acquired MEX3A RNA-Seq from 50 normal liver tissues and 373 liver cancer patients along with clinical data. We found that MEX3A was up-regulated in liver cancer which increased according to histological grade (p<0.001). MEX3A showed moderate diagnostic ability for liver cancer (AUC=0.837). Kaplan-Meier curves and Cox analysis revealed that the high expression of MEX3A was significantly associated with poor survival (OS and RFS) (p<0.001). Moreover, MEX3A was identified as an independent prognostic factor of liver cancer (p<0.001). Conclusions. MEX3A expression shows promise as an independent predictor of liver cancer prognosis.

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Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

Cited by 72 publications

References 231 publications

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

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

Peer Review #3 of "Clinical characteristics and prognostic value of MEX3A mRNA in liver cancer (v0.2)"

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