RNA editing affects cis‐regulatory elements and predicts adverse cancer survival

Wu, Yuan-Ming; Guo, Yan; Yu, Hui; Guo, Tao

doi:10.1002/cam4.4146

Cited by 5 publications

(3 citation statements)

References 65 publications

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“…Furthermore, NRIP1 is a classical mutated gene in EC cell lines [ 51 ], and its overexpression is a common cause driving EC and advanced myometrial invasion [ 52 , 53 ]. RNA editing levels of ZNF264 are greatly correlated with the clinical outcome of EC [ 54 ]. Overexpression of SOX12 was associated with a loss of tumor capsule [ 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Crosstalk of Redox-Related Subtypes, Establishment of a Prognostic Model and Immune Responses in Endometrial Carcinoma

Geng

Song

Zhong

et al. 2022

Cancers

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Redox plays a central part in the pathogeneses and development of tumors. We comprehensively determined the expression patterns of redox-related genes (RRGs) in endometrial carcinoma (EC) cohorts from public databases and identified four different RRG-related clusters. The prognosis and the characteristics of TME cell infiltration of RRGcluster C patients were worse than those of other RRG clusters. When it comes to the gene cluster, there were great differences in clinicopathology traits and immunocyte infiltration. The RRG score was calculated by Cox analyses, and an RRG-based signature was developed. The risk score performed well in the EC cohort. Samples were separated into two risk subgroups with the standard of the value of the median risk score. Low-risk patients had a better prognosis and higher immunogenicity. In addition, RRG score was closely associated with immunophenoscore, microsatellite instability, tumor mutation burden, tumor stem cell index, copy number variation and chemotherapy sensitivity. The nomogram accurately predicted the prognosis of patients, and our model showed better performance than other published models. In conclusion, we built a prognostic model of RRGs which can help to evaluate clinical outcomes and guide more effective treatment.

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Section: Discussionmentioning

confidence: 99%

Crosstalk of Redox-Related Subtypes, Establishment of a Prognostic Model and Immune Responses in Endometrial Carcinoma

Geng

Song

Zhong

et al. 2022

Cancers

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“…Survival, clinical relevance and ROC analysis confirmed that the risk model can accurately predict the prognosis of patients with glioma. Consistently, RNA-editing has been reported to impact the prognosis of multiple solid tumors, including but not limited to uterine corpus endometrial carcinoma (Wu et al, 2021), hepatocellular carcinoma (Chen et al, 2020), and esophageal squamous cell carcinoma (Qin et al, 2014). But given the heterogeneity between tumors and organ-selective expression of genes, the specific RNA-editing that affect prognosis vary by tumor.…”

Section: Prediction Of Chemotherapy Response In Different Risk Groupsmentioning

confidence: 96%

Prognostic RNA-editing signature predicts immune functions and therapy responses in gliomas

Zhang

et al. 2023

Front. Genet.

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Background: RNA-editing refers to post-transcriptional transcript alterations that lead to the formation of protein isoforms and the progression of various tumors. However, little is known about its roles in gliomas.Aim: The aim of this study is to identify prognosis-related RNA-editing sites (PREs) in glioma, and to explore their specific effects on glioma and potential mechanisms of action.Methods: Glioma genomic and clinical data were obtained from TCGA database and SYNAPSE platform. The PREs was identified with regression analyses and the corresponding prognostic model was evaluated with survival analysis and receiver operating characteristic curve. Functional enrichment of differentially expressed genes between risk groups was performed to explore action mechanisms. The CIBERSORT, ssGSEA, gene set variation analysis, and ESTIMATE algorithms were employed to assess the association between PREs risk score and variations of tumor microenvironment, immune cell infiltration, immune checkpoints, and immune responses. The maftools and pRRophetic packages were used to evaluate tumor mutation burden and predict drug sensitivity.Results: A total of thirty-five RNA-editing sites were identified as prognosis-related in glioma. Functional enrichment implied variation of immune-related pathways between groups. Notably, glioma samples with higher PREs risk score exhibited higher immune score, lower tumor purity, increased infiltration of macrophage and regulatory T cells, suppressed NK cell activation, elevated immune function score, upregulated immune checkpoint gene expression, and higher tumor mutation burden, all of which implied worse response to immune therapy. Finally, high-risk glioma samples are more sensitive to Z-LLNle-CHO and temozolomide, while the low-risk ones respond better to Lisitinib.Conclusion: We identified a PREs signature of thirty-five RNA editing sites and calculated their corresponding risk coefficients. Higher total signature risk score indicates worse prognosis and worse immune response and lower sensitivity to immune therapy. The novel PREs signature could help risk stratification, immunotherapy response prediction, individualized treatment strategy-making for glioma patients, and development of novel therapeutic approaches.

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“…RNA editing primarily takes the form of adenine‐to‐inosine (A‐to‐I) or cytosine‐to‐uracil (C‐to‐U) substitutions [12] . Studies have found that RNA editing can alter protein sequences, [13] affect drug sensitivity, [14] and cause poor cancer prognosis [15] . Because A‐to‐I subtitutions account for an overwhelming proportion of all RNA editing events (95 %), [16] we focused on A‐to‐I RNA editing in this study.…”

Section: Introductionmentioning

confidence: 99%

Genomic Variants Disrupt miRNA‐mRNA Regulation

Bai

Zhang

et al. 2022

Chemistry & Biodiversity

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Micro RNA (miRNA) and its regulatory effect on messenger RNA (mRNA) gene expression are a major focus in cancer research. Disruption in the normal miRNA-mRNA regulation network can result in serious cascading biological repercussions. In this study, we curated miRNA-related variants from major genomic consortiums and thoroughly evaluated how these variants could exert their effects by cross-validating with independent functional knowledge bases. Nearly all known variants (more than 664 million) categorized by type (germline, somatic, epigenetic) were mapped to the genomic regions involved in miRNA-mRNA binding (miRNA seeds and miRNA-mRNA 3'-UTR binding sequence). Subsets of miRNA-related variants supported by additional functional evidence, such as expression Quantitative Trait Loci (eQTL) and Genome-Wide Association Study (GWAS), were identified and scrutinized. Our results show that variants in miRNA seeds can substantially alter the composition of a miRNA's target mRNA set. Various functional analyses converged to reveal a post-transcriptional complex regulatory network where miRNA, eQTL, and RNA-binding protein intertwined to disseminate the impact of genomic variants. These results may potentially explain how certain variants affect disease/trait risks in genome wide association studies.

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RNA editing affects cis‐regulatory elements and predicts adverse cancer survival

Cited by 5 publications

References 65 publications

Crosstalk of Redox-Related Subtypes, Establishment of a Prognostic Model and Immune Responses in Endometrial Carcinoma

Crosstalk of Redox-Related Subtypes, Establishment of a Prognostic Model and Immune Responses in Endometrial Carcinoma

Prognostic RNA-editing signature predicts immune functions and therapy responses in gliomas

Genomic Variants Disrupt miRNA‐mRNA Regulation

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