RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Сен. 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.

Язык: Английский

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Targeting the RNA m6A modification for cancer immunotherapy

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Март 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.

Язык: Английский

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The m6A reader IGF2BP3 promotes acute myeloid leukemia progression by enhancing RCC2 stability

Experimental & Molecular Medicine, Год журнала: 2022, Номер 54(2), С. 194 - 205

Опубликована: Фев. 1, 2022

Abstract N6-methyladenosine (m6A) is the most abundant posttranscriptional modification of mRNA in eukaryotes. Recent evidence suggests that dysregulated m6A-associated proteins and m6A modifications play a pivotal role initiation progression diseases such as cancer. Here, we identified IGF2BP3 specifically overexpressed acute myeloid leukemia (AML), subtype associated with poor prognosis high genetic risk. required for maintaining AML cell survival an m6A-dependent manner, knockdown dramatically suppresses apoptosis, reduces proliferation, impairs leukemic capacity cells vitro vivo. Mechanistically, interacts RCC2 stabilizes expression m6A-modified RNA. Thus, provided compelling demonstrating reader contributes to tumorigenesis can serve target development cancer therapeutics.

Язык: Английский

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Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: impacts on therapeutic resistance

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Июль 18, 2022

Abstract The resistance of tumor cells to therapy severely impairs the efficacy treatment, leading recurrence and metastasis various cancers. Clarifying underlying mechanisms therapeutic may provide new strategies for overcoming cancer resistance. N6-methyladenosine (m6A) is most prevalent RNA modification in eukaryotes, involved regulation splicing, translation, transport, degradation, stability processing, thus affecting several physiological processes progression. As a novel type multifunctional non-coding RNAs (ncRNAs), circular (circRNAs) have been demonstrated play vital roles anticancer therapy. Currently, accumulating studies revealed mutual m6A circRNAs, their interaction can further influence sensitivity treatment. In this review, we mainly summarized recent advances circRNAs modulation resistance, as well interplay potential mechanisms, providing promising insights future directions reversal cancer.

Язык: Английский

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New insight into circRNAs: characterization, strategies, and biomedical applications

Experimental Hematology and Oncology, Год журнала: 2023, Номер 12(1)

Опубликована: Окт. 12, 2023

Abstract Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput sequencing and experimental technologies have enabled the extensive identification characterization circRNAs, such as novel types biogenesis, tissue-specific cell-specific expression patterns, epigenetic regulation, translation potential, localization metabolism. Increasing evidence has revealed that participate in diverse cellular processes, their dysregulation is involved pathogenesis various diseases, particularly cancer. In this review, we systematically discuss databases, challenges for circRNA discovery, new insight into strategies used studies biomedical applications. Although recent advanced understanding knowledge approaches annotation, functional applications continuously needed to provide insights circRNAs. The emergence circRNA-based protein strategy will be promising direction field biomedicine.

Язык: Английский

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Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner

Redox Biology, Год журнала: 2024, Номер 69, С. 103026 - 103026

Опубликована: Янв. 4, 2024

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves methyl donor and plays role reducing Hcy. However, effects mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected Hcy (400 μg/kg) through vena caudalis, (2.5 % w/v) was supplemented via drinking water for 14 days. supplementation could attenuate Y maze novel object recognition tests by repairing brain injury. Meanwhile, microglial activation observed to be inhibited using immunofluorescence sholl analysis. Secondly, HMC3 cells treated betaine, which found decrease ROS level, ameliorate cell membrane rupture, reduce release LDH, IL-18 IL-1β, damage microglia neurons. Mechanistically, alleviates inhibiting pyroptosis expressions NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β. treatment can increase SAM/SAH ratio, confirming its enhancement methylation capacity. Furthermore, enhance N6-methyladenosine (m6A) modification NLRP3 mRNA, reduced mRNA stability increasing expression m6A reader YTH RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 reverse inhibitory effect pyroptosis. Our data demonstrated that attenuated suppressing NLRP3/caspase-1/GSDMD pathway m6A-YTHDF2-dependent manner.

Язык: Английский

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METTL16 promotes glycolytic metabolism reprogramming and colorectal cancer progression

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Июнь 20, 2023

Abstract Background Glycolysis is the key hallmark of cancer and maintains malignant tumor initiation progression. The role N6-methyladenosine (m6A) modification in glycolysis largely unknown. This study explored biological function m6A methyltransferase METTL16 glycolytic metabolism revealed a new mechanism for progression Colorectal (CRC). Methods expression prognostic value was evaluated using bioinformatics immunohistochemistry (IHC) assays. functions CRC analyzed vivo vitro. Glycolytic assays were used to verify Suppressor glucose by autophagy (SOGA1). protein/RNA stability, RNA immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP) pull-down explore potential molecular mechanisms. Results SOGA1 direct downstream target involved mediated significantly enhances mRNA stability via binding “reader” protein insulin-like growth factor 2 1 (IGF2BP1). Subsequently, promotes AMP-activated kinase (AMPK) complex ubiquitination, inhibits its phosphorylation, thus upregulates pyruvate dehydrogenase 4 (PDK4), crucial controlling metabolism. Moreover, Yin Yang (YY1) can transcriptionally inhibit cells directly promoter. Clinical data showed that positively correlated PDK4, associated with poor prognosis patients. Conclusions Our findings suggest METTL16/SOGA1/PDK4 axis might be promising therapeutic targets CRC.

Язык: Английский

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METTL3 protects METTL14 from STUB1‐mediated degradation to maintain m⁶A homeostasis

EMBO Reports, Год журнала: 2023, Номер 24(3)

Опубликована: Янв. 4, 2023

Язык: Английский

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Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Фев. 27, 2023

Background Ovarian reserve is an important factor determining female reproductive potential. The number and quality of oocytes in patients with diminished ovarian (DOR) are reduced, even if vitro fertilization-embryo transfer (IVF-ET) used to assist their pregnancy, the clinical pregnancy rate live birth still low. Infertility caused by reduced one most difficult problems field reproduction. Follicular fluid microenvironment for oocyte survival, metabolic characteristics follicular can be obtained metabolomics technology. By analyzing status fluid, we hope find factors that affect new diagnostic markers provide clues early detection intervention DOR. Methods In this research, 26 infertile women DOR 28 volunteers normal receiving IVF/ET were recruited, samples collected a nontargeted metabonomic study. orthogonal partial least squares discriminant analysis model was understand separation trend two groups, KEGG analyze possible pathways involved differential metabolites, random forest algorithm establish model. Results 12 upregulated 32 downregulated metabolites detected analysis, mainly including amino acids, indoles, nucleosides, organic steroids, phospholipids, fatty acyls, oxygen compounds. Through these aminoacyl-tRNA biosynthesis, tryptophan metabolism, pantothenate CoA purine metabolism. AUC value based on top 10 0.9936. Conclusion shows unique characteristics. These data us rich biochemical information research basis exploring pathogenesis predicting function.

Язык: Английский

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The emerging importance role of m6A modification in liver disease

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 162, С. 114669 - 114669

Опубликована: Апрель 8, 2023

N6-methyladenosine (m6A) modification, as one of the most common types inner RNA modification in eukaryotes, plays a multifunctional role normal and abnormal biological processes. This type is modulated by m6A writer, eraser reader, which turn impact various processes metabolism, such processing, translation, nuclear export, localization decay. The current academic view holds that exerts crucial post-transcriptional modulation gene expression, involved multiple cellular functions, developmental disease However, potential molecular mechanism specific development liver have not been fully elucidated. In our review, we summarized latest research progress on disease, explored how these novel findings reshape knowledge metabolism. addition, also illustrated effect regeneration to prompt further exploration physiology pathology, providing new insights references for search therapeutic targets disease.

Язык: Английский

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