Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(9), P. 1660 - 1677.e10

Published: March 22, 2022

Language: Английский

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m6A modification: recent advances, anticancer targeted drug discovery and beyond

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

Published: Feb. 14, 2022

Abstract Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches modern discovery platforms used in an attempt to develop m6A-targeted drugs. Here, we provide update latest findings on critical roles cancer progression, summarize rational sources for agents from medicines computer-based chemosynthetic compounds. This review highlights potential targeting treatment proposes advantage artificial intelligence (AI) m6A-targeting Graphical abstract Three stages discovery: medicine-based natural products, chemical or synthesis, (AI)-assisted future.

Language: Английский

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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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The roles and implications of RNA m6A modification in cancer

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(8), P. 507 - 526

Published: May 23, 2023

Language: Английский

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FTO mediates LINE1 m ⁶ A demethylation and chromatin regulation in mESCs and mouse development

Science, Journal Year: 2022, Volume and Issue: 376(6596), P. 968 - 973

Published: May 5, 2022

-methyladenosine (m

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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Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

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FTO in cancer: functions, molecular mechanisms, and therapeutic implications

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(7), P. 598 - 614

Published: March 25, 2022

Language: Английский

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Targeting memory T cell metabolism to improve immunity

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(1)

Published: Jan. 3, 2022

Vaccination affords protection from disease by activating pathogen-specific immune cells and facilitating the development of persistent immunologic memory toward vaccine-specific pathogen. Current vaccine regimens are often based on efficiency acute response, not necessarily generation cells, in part because mechanisms underlying efficient remain incompletely understood. This Review describes recent advances defining T cell metabolism how these might be altered patients affected mitochondrial diseases or metabolic syndrome, who show higher susceptibility to recurrent infections rates failure. It discusses this new understanding could add way we think about memory, development, cancer immunotherapy.

Language: Английский

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YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(2), P. 255 - 266

Published: Jan. 19, 2023

Language: Английский

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