LNC942 promoting METTL14-mediated m6A methylation in breast cancer cell proliferation and progression

Oncogene, Год журнала: 2020, Номер 39(31), С. 5358 - 5372

Опубликована: Июнь 23, 2020

Язык: Английский

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Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response

Nucleic Acids Research, Год журнала: 2021, Номер 49(10), С. 5779 - 5797

Опубликована: Май 1, 2021

Abstract Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating post-translational modifications (PTMs), leading to rapid efficient induction of thousands genes involved variety biological processes including repair. Mechanistically, promotes SUMOylation through activating ERK/JNK signaling, inhibition m6A activity blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated hematopoietic stem/progenitor (HSPCs) vivo mice, suggesting physiological this molecular pathway stability HSPCs. Together, our study uncovers mechanism involving PTMs increased protect genomic response ROS.

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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Role of m6A writers, erasers and readers in cancer

Experimental Hematology and Oncology, Год журнала: 2022, Номер 11(1)

Опубликована: Авг. 9, 2022

Abstract The N(6)-methyladenosine (m6A) modification is the most pervasive of human RNAs. In recent years, an increasing number studies have suggested that m6A likely plays important roles in cancers. Many demonstrated involved biological functions cancer cells, such as proliferation, invasion, metastasis, and drug resistance. addition, closely related to prognosis patients. this review, we highlight advances understanding function various We emphasize importance progression look forward describe future research directions.

Язык: Английский

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RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Янв. 21, 2022

RNA demethylase ALKBH5 takes part in the modulation of N

Язык: Английский

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