Biological roles of RNA m5C modification and its implications in Cancer immunotherapy

Biomarker Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: April 1, 2022

Abstract Epigenetics including DNA and RNA modifications have always been the hotspot field of life sciences in post-genome era. Since first mapping N6-methyladenosine (m 6 A) discovery its widespread presence mRNA, there are at least 160-170 discovered. These methylations occur different types, their distribution is species-specific. 5-methylcytosine 5 C) has found rRNA tRNA representative organisms from all kinds species. As reversible epigenetic modifications, m C affect fate modified molecules play important roles various biological processes stability control, protein synthesis, transcriptional regulation. Furthermore, accumulative evidence also implicates role tumorigenesis. Here, we review latest progresses how it regulated by corresponding “writers”, “readers” “erasers” proteins, as well potential molecular mechanism tumorigenesis cancer immunotherapy.

Language: Английский

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The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 27, 2022

RNA modification of m6A/m5C/m1A contributes to the occurrence and development cancer. Consequently, this study aimed investigate functions regulated genes in prognosis immune microenvironment hepatocellular carcinoma (HCC). The expression levels 45 HCC tissues were determined. functional mechanisms protein–protein interaction network investigated. Cancer Genome Atlas (TCGA) gene set was categorized based on genes, survival analysis used determine relationship between overall patients subgroups. Cox least absolute shrinkage selection operator (LASSO) regression analyses construct risk model nomogram for genes. relationships subsets cell infiltration analyzed using CIBERSORT. involved mRNA modifications, methylation, stability, other processes. There a statistically significant difference cluster1 cluster2 groups by m6A/m5C/m1A. significantly better than that patients. differences two cluster terms fustat status, grade, clinical stage, T stage comprised overexpression YBX1, ZC3H13, YTHDF1, TRMT10C, YTHDF2, RRP8, TRMT6, LRPPRC, IGF2BP3, which contributed poor high-risk score associated with prognosis, M an independent factor High-risk included spliceosome, degradation, DNA replication, among others, closely related stromal score, CD4 memory resting cells, M0 macrophages, M1 mast activated follicular helper cells. In conclusion, subgroup are expected be new tools assessing

Language: Английский

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An m6A/m5C/m1A/m7G-Related Long Non-coding RNA Signature to Predict Prognosis and Immune Features of Glioma

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: May 26, 2022

Background: Gliomas are the most common and fatal malignant type of tumor central nervous system. RNA post-transcriptional modifications, as a frontier hotspot in field epigenetics, have attracted increased attention recent years. Among such methylation is abundant, encompasses N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1 methyladenosine (m1A), 7-methylguanosine (m7G) methylation. Methods: RNA-sequencing data from healthy tissue low-grade glioma samples were downloaded The Cancer Genome Atlas database along with clinical information mutation glioblastoma samples. Forty-nine m6A/m5C/m1A/m7G-related genes identified an m6A/m5C/m1A/m7G-lncRNA signature co-expressed long non-coding RNAs selected. Least absolute shrinkage selection operator Cox regression analysis was used to identify 12 lncRNAs associated prognostic characteristics their correlation immune function drug sensitivity analyzed. Furthermore, Chinese Glioma dataset for model validation. Results: A total (AL080276.2, AC092111.1, SOX21-AS1, DNAJC9-AS1, AC025171.1, AL356019.2, AC017104.1, AC099850.3, UNC5B-AS1, AC006064.2, AC010319.4, AC016822.1) construct survival prognosis model, which had good independent prediction ability patients glioma. Patients divided into low high m6A/m5C/m1A/m7G-LS groups, latter poor prognosis. In addition, enabled improved interpretation results enrichment analysis, well informing immunotherapy response different subgroups. Conclusion: this study we constructed established nomogram can accurately predict provides direction toward promising strategies future.

Language: Английский

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A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 24, 2022

Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model evaluating risk LUAD based on hypoxia, immunity, epithelial-mesenchymal transition (EMT) gene signatures. Methods: In this study, we used data from TCGA-LUAD training cohort GSE68465 GSE72094 validation cohorts. Immunotherapy datasets GSE135222, GSE126044, IMvigor210 were obtained previous study. Using bioinformatic machine algorithms, established immune, EMT signatures, which was then divide patients into high low groups. We analyzed differences in enriched pathways between two groups, following investigated whether score correlated stemness scores, genes related m6A, m5C, m1A m7G modification, immune microenvironment, immunotherapy response, multiple anti-cancer drug sensitivity. Results: Overall differed significantly high-risk low-risk groups (HR = 4.26). The AUCs predicting 1-, 3-, 5-year 0.763, 0.766, 0.728, respectively. dataset, HR 2.03, while 0.69, 0.651, 0.618, corresponding values dataset an 2.36 0.653, 0.662, 0.749, could independently predict OS LUAD, highly scores numerous modification-related genes. Furthermore, microenvironment characteristics. GSE135222 4.26 AUC 0.702. Evaluation GSE126044 cohorts indicated that PD-1/PD-LI inhibitor treatment may be therapy various drugs scores. Conclusion: Our developed signatures can aid prognosis guiding LUAD.

Language: Английский

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Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma

Journal of Immunology Research, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 40

Published: Oct. 14, 2022

Cuproptosis is a newly discovered copper-independent cell death modality, and limited evidence suggests the critical implications in human cancers. Nonetheless, clinical impacts of cuproptosis-relevant lncRNAs lung adenocarcinoma (LUAD) remain largely ill-defined. The present study was aimed at defining lncRNA signature for LUAD discuss utility.We collected transcriptome expression profiling, information, somatic mutation, copy number variations from TCGA-LUAD cohort retrospectively. genetic alterations cuproptosis genes were systematically assessed across LUAD, screened LASSO prognostic model. Genomic alterations, immunological stemness features, therapeutic sensitivity studied with series computational approaches.Cuproptosis displayed aberrant widespread genomic potentially modulated by m6A/m5C/m1A RNA modification mechanisms. We defined signature, reliable efficacy predicting outcomes. High-risk subset higher mutations, CNVs, TMB, SNV neoantigens, aneuploidy score, CTA homologous recombination defects, intratumor heterogeneity, cytolytic activity, CD8+ T effector, antigen processing machinery, proving that this might benefit immunotherapy. Increased indexes activity oncogenic pathways contribute to undesirable outcomes high-risk subset. Additionally, patients generally exhibited response chemotherapeutic agents (cisplatin, etc.). also predicted several small molecule compounds (GSK461364, KX2-391, etc.) treating subset.Accordingly, offers an efficient approach identify characterize diverse prognosis, treatment thus assisting personalized therapy.

Language: Английский

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Vital roles of m5C RNA modification in cancer and immune cell biology

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 31, 2023

RNA modification plays an important role in epigenetics at the posttranscriptional level, and 5-methylcytosine (m 5 C) has attracted increasing attention recent years due to improvement m C site detection methods. By influencing transcription, transportation translation, of mRNA, tRNA, rRNA, lncRNA other RNAs been proven affect gene expression metabolism is associated with a wide range diseases, including malignant cancers. modifications also substantially impact tumor microenvironment (TME) by targeting different groups immune cells, B T macrophages, granulocytes, NK dendritic cells mast cells. Alterations cell expression, infiltration activation are highly linked malignancy patient prognosis. This review provides novel holistic examination C-mediated cancer development examining exact mechanisms underlying oncogenicity summarizing biological effects on as well Understanding methylation-related tumorigenesis can provide useful insights for diagnosis treatment cancer.

Language: Английский

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Prognostic Value and Genome Signature of m6A/m5C Regulated Genes in Early-Stage Lung Adenocarcinoma

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6520 - 6520

Published: March 30, 2023

RNA modifications implicate pathological and prognosis significance in cancer development progression, of which, m6A m5C are representative regulators. These could produce effects on the function other by regulating gene expression. Thus, this study, we aimed to explore correlation between m6A/m5C regulators early-stage lung adenocarcinoma (LUAD). Only LUAD samples were included investigation, RNA-seq dataset The Cancer Genome Atlas (TCGA) cohort was utilized evaluate expression 37 regulated genes. Based level these genes, patients divided into 2 clusters, which performed consensus clustering, subtypes had significantly different prognostic outcomes (p < 0.001). Cluster1, has a better prognosis, characterized C3 (inflammatory) immune subtype, low infiltration, chemokine expression, major histocompatibility complex (MHC) checkpoint molecule Furthermore, compared with cluster1, cluster2 showed T cell exhaustion state, high cells, such as CD8+ cytotoxic lymphocytes, NK so on. In addition, tumor mutational burden (TMB) numerous significant mutated oncogene suppressor WNT10B, ERBB4, SMARCA4, TP53, CDKN2A A total 19 genes mostly related upregulated 0.05), showing positive mRNA predictive risk model constructed using Cox LASSO (least absolute shrinkage selection operator) regression analysis. Finally, seven-gene model, comprising METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, NSUN7, stratify = 0.0049, AUC 0.791). high-risk score associated poorer prognosis. This also validated two additional GEO datasets: GSE72094 0.011, 0.736) GSE50081 0.012, 0.628). summary, it established that m6A/m5C-regulated crosstalk LUAD. By interacting modification disturbs DNA replication microenvironment (TIME). may be critical tool for assessment

Language: Английский

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Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8)

Published: April 1, 2024

Abstract Research indicates that there are links between m6A, m5C and m1A modifications the development of different types tumours. However, it is not yet clear if these involved in prognosis LUAD. The TCGA‐LUAD dataset was used as for signature training, while validation cohort created by amalgamating publicly accessible GEO datasets including GSE29013, GSE30219, GSE31210, GSE37745 GSE50081. study focused on 33 genes regulated or (mRG), which were to form mRGs clusters mRG differentially expressed (mRG‐DEG clusters). Our subsequent LASSO regression analysis trained m6A/m5C/m1A‐related lncRNA (mRLncSig) using lncRNAs exhibited differential expression among mRG‐DEG had prognostic value. model's accuracy underwent via Kaplan–Meier analysis, Cox regression, ROC tAUC evaluation, PCA examination nomogram predictor validation. In evaluating immunotherapeutic potential signature, we employed multiple bioinformatics algorithms concepts through various analyses. These included seven newly developed immunoinformatic algorithms, well evaluations TMB, TIDE immune checkpoints. Additionally, identified validated promising agents target high‐risk mRLncSig To validate real‐world pattern mRLncSig, real‐time PCR carried out human LUAD tissues. signature's ability perform pan‐cancer settings also evaluated. a 10‐lncRNA have power cohort. Real‐time applied verify actual manifestation each gene real world. immunotherapy revealed an association status. found be closely linked several checkpoints, such IL10, IL2, CD40LG, SELP, BTLA CD28, could appropriate targets Among patients, our 12 candidate drugs verified gemcitabine most significant one effective treating discovered some play crucial role certain cancer types, thus, may require further attention future studies. According findings this study, use has aid forecasting serve immunotherapy. Moreover, assist identifying therapeutic more effectively.

Language: Английский

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The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response

Theranostics, Journal Year: 2022, Volume and Issue: 12(8), P. 3946 - 3962

Published: Jan. 1, 2022

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components the cellular machinery for its profit, circumventing natural defense mechanisms triggered by infected cell. successful completion replicative viral cycle within a cell depends function versus defenses. Non-coding RNAs (ncRNAs) important modulators, either promoting or preventing progression infections. Among these ncRNAs, long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators response during infection human host cells single stranded viruses. However, role in coronaviruses such SARS-CoV-2 remains uncharacterized. Methods: In present work, we performed transcriptomic study cohort patients with different load analyzed involvement supporting regulatory networks interaction RNA-binding proteins (RBPs). Results: Our results revealed existence infection-dependent pattern transcriptional up-regulation which specific integral component. To determine lncRNAs, correlation analysis complemented validated interactions between RBPs. This combination silico association studies experimental evidence allowed us identify lncRNA signature composed six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, U62317.2 associated regulation infection. Conclusions: We propose competition mechanism genome sequestering RBPs that modulates interferon surveillance nonsense-mediated decay (NMD).

Language: Английский

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The prognostic value and immune landscape of a cuproptosis-related lncRNA signature in head and neck squamous cell carcinoma

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Background: Cuproptosis has been recognized as a novel regulatory cell death, which confirmed to promote the occurrence and development of tumors. However, whether cuproptosis-related lncRNA an impact on prognosis squamous carcinoma head neck (HNSCC) is still unclear. Methods: In total, 501 HNSCC tumor samples 44 normal were downloaded from TCGA database. Cuproptosis-related lncRNAs obtained by co-expressed analysis. We got prognostic that was associated with cuproptosis using univariate Cox regression analysis LASSO regression. Then we constructed validated signature analyzed immune landscape signature. Results: The Prognostic Signature based 10 including AC090587.1, AC004943.2, TTN-AS1, AL162458.1, AC106820.5, AC012313.5, AL132800.1, WDFY3-AS2, CDKN2A-DT, AL136419.3. results overall survival, risk score distribution, survival status in low-risk group better than those high-risk group. addition, all checkpoint genes involved significantly different between two groups (p < 0.05). positively correlated Eosinophils. M0 M2 phenotype macrophages, mast cells activated, NK negatively related B naive, resting, plasma cells, CD8T T follicular helper, (Tregs). Consensus clustering identified molecular subtypes HNSC. More concentrated Cluster1, had higher Tumor Immune Dysfunction Exclusion (TIDE) Single Nucleotide Polymorphisms (SNP) alternation Cluster2. Conclusion: Our study elucidated correlation HNSCC, may provide references for further research exploration mechanism functions HNSCC.

Language: Английский

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