RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

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Targeting the RNA m6A modification for cancer immunotherapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: March 16, 2022

Abstract N 6 -methyladenosine (m A) is the most abundant epigenetic modification of RNA, and its dysregulation drives aberrant transcription translation programs that promote cancer occurrence progression. Although defective gene regulation resulting from m A often affects oncogenic tumor-suppressing networks, can also modulate tumor immunogenicity immune cells involved in anti-tumor responses. Understanding this counterintuitive concept aid design new drugs target to potentially improve outcomes immunotherapies. Here, we provide an up-to-date comprehensive overview how modifications intrinsically affect alterations cell extrinsically responses microenvironment (TME). We review strategies for modulating endogenous immunity discuss challenge reshaping TME. Strategies include: combining specific efficient inhibitors against regulators with checkpoint blockers; generating effective programmable gene-editing system enables manipulation individual sites; establishing enhance T or natural killer cells; using nanoparticles specifically tumor-associated macrophages (TAMs) deliver messenger RNA small interfering A-related molecules repolarize TAMs, enabling them remodel The goal help field understand shape TME so better immunotherapy be designed developed.

Language: Английский

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m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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RNA-mediated immunotherapy regulating tumor immune microenvironment: next wave of cancer therapeutics

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 21, 2022

Abstract Accumulating research suggests that the tumor immune microenvironment (TIME) plays an essential role in regulation of growth and metastasis. The cellular molecular nature TIME influences cancer progression metastasis by altering ratio immune- suppressive versus cytotoxic responses vicinity tumor. Targeting or activating components show a promising therapeutic avenue to combat cancer. success immunotherapy is both astounding unsatisfactory clinic. Advancements RNA-based technology have improved understanding complexity diversity its effects on therapy. TIME-related RNA regulators could be targets for anticancer immunotherapy. In this review, we discuss available immunotherapies targeting TIME. More importantly, summarize potential various therapeutics clinically treatment. RNA-dependent TIME, as monotherapy combined with other evolving therapeutics, might beneficial patients’ treatment near future.

Language: Английский

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Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 6, 2022

Abstract The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, immunosuppression. One the most common RNA N6-methyladenosine (m 6 A) methylation, widely involved regulation physiological pathological processes, including development. Compelling evidence indicates that m A methylation regulates transcription protein expression through shearing, export, translation, processing, thereby participating dynamic evolution TME. Specifically, methylation-mediated adaptation to phenotypic shift immune cells synergistically promote formation an immunosuppressive supports proliferation metastasis. In this review, we have focused on involvement tumor-adaptive described detailed linking change cell biological functions. view collective data, advocate treating as complete ecosystem components crosstalk with each other achieve adaptive changes. Finally, describe potential utility methylation-targeted therapies immunotherapy clinical applications challenges faced, aim advancing research.

Language: Английский

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Biological and pharmacological roles of m6A modifications in cancer drug resistance

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Dec. 14, 2022

Abstract Cancer drug resistance represents the main obstacle in cancer treatment. Drug-resistant cancers exhibit complex molecular mechanisms to hit back therapy under pharmacological pressure. As a reversible epigenetic modification, N 6 -methyladenosine (m A) RNA modification was regarded be most common modification. methyltransferases (writers), demethylases (erasers), and m A-binding proteins (readers) are frequently disordered several tumors, thus regulating expression of oncoproteins, enhancing tumorigenesis, proliferation, development, metastasis. The review elucidated underlying role A resistance. Alteration affected efficacy by restructuring multidrug efflux transporters, drug-metabolizing enzymes, anticancer targets. Furthermore, variation resulted DNA damage repair, downstream adaptive response (apoptosis, autophagy, oncogenic bypass signaling), cell stemness, tumor immune microenvironment, exosomal non-coding RNA. It is highlighted that small molecules targeting regulators have shown significant potential for overcoming different categories. Further inhibitors activators A-modified expected provide novel drugs, delivering therapeutic addressing challenge clinical

Language: Английский

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m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(3)

Published: March 1, 2022

Abstract Background The intervertebral disc (IVD) degeneration is the leading cause of low back pain, which accounts for a main disability. N 6‐methyladenosine (m6A) most abundant internal modification in eukaryotic messenger RNAs and involved various diseases cellular processes by modulating mRNA fate. However, critical role m6A regulation IVD remains unclear. Nucleus pulposus cell (NPC) senescence progression degeneration. Here, we uncovered explored regulatory mechanism NPC during Methods Identification was based on analysis tissue samples model. ALKBH5 upregulation inducing confirmed functional experiments vivo vitro. ChIP‐qPCR DNA‐Pulldown were used to reveal increased regulated KDM4A‐mediated H3K9me3. Furthermore, Me‐RIP‐seq performed identify hypomethylation DNMT3B transcripts senescent NPCs. Stability showed that expression enhanced less YTHDF2 recognition promoted via E4F1 methylation vitro analyses. Results Expression senescence, due decreased H3K9me3 modification. Functionally, causes demethylating turn promoting its following degradation transcript vivo. Increased promotes development mechanistically methylating CpG islands at promoter region thus restraining transcription expression. Conclusions Collectively, our findings an epigenetic interplay degeneration, presenting pro‐senescence hypomethylation, highlighting therapeutic potential targeting m6A/DNMT3B/E4F1 axis treating

Language: Английский

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Roles and therapeutic implications of m6A modification in cancer immunotherapy

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

Published: March 7, 2023

Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), m6A recognition proteins (readers). Aberrant regulation pivotal for tumorigenesis, progression, invasion, metastasis, apoptosis malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized 2018 Nobel Prize Medicine Physiology. However, not all patients response to ICI therapy, which thought be result intricate immune escape mechanisms. Recently, numerous suggested novel role tumor evasion. Herein, we review relevant mechanisms regulators regulating various key signaling pathways biology how modifications regulate expression checkpoints, opening new window understand roles In addition, highlight prospects development directions future combined immunotherapy strategies based on targeting, providing promoting treatment outcomes inhibitors.

Language: Английский

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The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: July 6, 2023

Abstract Tumor initiation, progression, and response to therapies depend a great extent on interactions between malignant cells the tumor microenvironment (TME), which denotes cancerous/non-cancerous cells, cytokines, chemokines, various other factors around tumors. Cancer as well stroma can not only obtain adaption TME but also sculpt their through series of signaling pathways. The post-translational modification (PTM) eukaryotic by small ubiquitin-related modifier (SUMO) proteins is now recognized key flexible pathway. Proteins involved in tumorigenesis guiding several biological processes including chromatin organization, DNA repair, transcription, protein trafficking, signal conduction rely SUMOylation. purpose this review explore role that SUMOylation plays formation reprogramming, emphasize importance targeting intervene discuss potential inhibitors (SUMOi) ameliorating prognosis.

Language: Английский

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