Transcriptome‐Wide Analysis Reveals the Landscape of Aberrant Alternative Splicing Events in Liver Cancer

Li, Shengli; Hu, Zhixiang; Zhao, Yingjun; Huang, Shenglin; He, Xianghuo

doi:10.1002/hep.30158

Cited by 98 publications

(103 citation statements)

References 43 publications

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“…The downregulated RBPs were mainly enriched in the mRNA metabolic process, RNA processing, regulation of translation, TGF-beta signaling pathway, and Toll-like receptor signaling pathway. In recent years, a large number of studies, have reported the role of aberrant RNA metabolism and RNA processing in various diseases (Li et al, 2017(Li et al, , 2018Li S. et al, 2019;. RNA processing factors were shown to have increased expression in poorly differentiated non-small-cell lung cancer cells (Geles et al, 2016).…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…The ASEs of individual genes can affect several important players in tumor initiation and progression (6,30,(36)(37)(38). For instance, the δ isoform of Max could promote glioma cell proliferation by enhancing functions of MYC in GBM harboring EGFRvIII mutation (39); 2 CD97 isoforms, EGF-1,2,5 and EGF-1,2,3,5, could promote growth, migration, metastasis, and angiogenesis in GBM (40); and an aberrant splicing of cyclin-dependent kinase-associated protein phosphatase, KAP, increases proliferation and migration in GBM (30).…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

RNA processing genes characterize RNA splicing and further stratify lower-grade glioma

Chai¹,

Li²,

Zhang³

et al. 2019

JCI Insight

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“…The editing of SLC22A3 transcript can induce the down-expression of SLC22A3 protein, which contributes to the early invasion in familial esophageal squamous cell carcinoma (9). Second, about 95% of multi-exon genes produce different transcripts through alternative splicing (10,11), which is common in human liver cancer (12). RNA editing occurring in splicing sites or splicing regulatory elements possibly affects the variable splicing processes of RNA.…”

Section: Introductionmentioning

confidence: 99%

Genomic Identification of RNA Editing Through Integrating Omics Datasets and the Clinical Relevance in Hepatocellular Carcinoma

Chen

Wang

et al. 2020

Front. Oncol.

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RNA editing is a widespread post-transcriptional mechanism to introduce single nucleotide changes to RNA in human cancers. Here, we characterized the global RNA editing profiles of 373 hepatocellular carcinoma (HCC) and 50 adjacent normal liver samples from The Cancer Genome Atlas (TCGA) and revealed that most editing events tend to occur in minor percentage of samples with moderate editing degrees (20-30%). Moreover, these RNA editing prefer to be A-to-I RNA editing in protein coding genes, especially in 3 ′ UTR regions. Considering the association between DNA mutation and RNA editing, our analysis found that RNA editing maybe a complementary event for DNA mutation of HCC risk genes in HCC patients. We next identified 454 HCC-related editing sites, and many locate on the same genes with the same editing patterns. The functional consequences of editing revealed 2,086 functional editing sites and demonstrated that most editing in coding regions are non-synonymous variations. Furthermore, our results showed that editing in the 3 ′ UTR regions tend to influence miRNA-target binding, and the editing degree seems to be negatively correlated with gene expression. Finally, we found that 46 HCC-related editing sites with consequence are able to distinguish the prognosis differences of HCC patients, suggesting their clinical relevance. Together, our results highlight RNA editing as a valuable molecular resource for investigating HCC mechanisms and clinical treatments.

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Transcriptome‐Wide Analysis Reveals the Landscape of Aberrant Alternative Splicing Events in Liver Cancer

Cited by 98 publications

References 43 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

RNA processing genes characterize RNA splicing and further stratify lower-grade glioma

Genomic Identification of RNA Editing Through Integrating Omics Datasets and the Clinical Relevance in Hepatocellular Carcinoma

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