The role of m6A RNA methylation in cancer metabolism

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

Published: Jan. 12, 2022

Abstract Metabolic reprogramming is one of the main characteristics malignant tumors, which due to flexible changes cell metabolism that can meet needs growth and maintain homeostasis tissue environments. Cancer cells obtain metabolic adaptation through a variety endogenous exogenous signaling pathways, not only promote cancer cells, but also start transformation process adapt tumor microenvironment. Studies show m6A RNA methylation widely involved in recombination cells. In eukaryotes, most abundant modification mRNA, almost all cycle stages, including regulation transcription, maturation, translation, degradation stability mRNA. M6A be physiological pathological processes, cancer. this review, we discuss role plays metabolism-related molecules aiming importance targeting regulating metabolism.

Language: Английский

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The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Jan. 18, 2021

Abstract RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances been made in understanding the functional role regulating coding and non-coding processing function, which turn thoroughly shape distinct They affect diverse biological processes, correct deposition many these is required for normal development. Alterations their are implicated several diseases, including cancer. In this Review, we focus on occurrence N 6 -methyladenosine (m A), 5-methylcytosine 5 C) pseudouridine (Ψ) RNAs describe physiopathological We will highlight latest insights into mechanisms how influence tumour development, maintenance, progression. Finally, summarize development small molecule inhibitors that target specific writers or erasers to rewind epitranscriptome a cancer cell therapeutic potential.

Language: Английский

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ALKBH5 suppresses malignancy of hepatocellular carcinoma via m6A-guided epigenetic inhibition of LYPD1

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Aug. 10, 2020

Abstract Background N6-methyladenosine (m 6 A) modification is an emerging layer of epigenetic regulation which widely implicated in the tumorigenicity hepatocellular carcinoma (HCC), offering a novel perspective for investigating molecular pathogenesis this disease. The role AlkB homolog 5 (ALKBH5), one m A demethylases, has not been fully explored HCC. Here we clarify biological profile and potential mechanisms ALKBH5 Methods Expression its correlation with clinicopathological characteristics HCC were evaluated using tissue microarrays online datasets. And effects determined vitro vivo. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined (RNA-seq), following dot blot, MeRIP-qPCR, RIP-qPCR or dual luciferase reporter assays employed to screen validate candidate targets ALKBH5. Results We demonstrated that was down-regulated HCC, decreased expression independent prognostic factor worse survival patients. Functionally, suppressed proliferation invasion capabilities cells Mechanistically, ALKBH5-mediated demethylation led post-transcriptional inhibition LY6/PLAUR Domain Containing 1 (LYPD1), could be recognized stabilized by effector IGF2BP1. In addition, identified LYPD1 induced oncogenic behaviors tumors contrast Dysregulation ALKBH5/LYPD1 axis impelled progression Conclusion Our study reveals ALKBH5, characterized as tumor suppressor, attenuates via A-dependent manner cells. findings enrich landscape A-modulated malignancy, provide new insights into biomarkers therapeutic treatment.

Language: Английский

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The m6A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function

Redox Biology, Journal Year: 2020, Volume and Issue: 38, P. 101801 - 101801

Published: Nov. 19, 2020

The biological functions of N6-methyladenosine (m6A) RNA methylation are mainly dependent on the reader; however, its role in lung tumorigenesis remains unclear. Here, we have demonstrated that m6A reader YT521-B homology domain containing 2 (YTHDC2) is frequently suppressed adenocarcinoma (LUAD). Downregulation YTHDC2 was associated with poor clinical outcome LUAD. decreased a spontaneous LUAD mouse model. Moreover, exhibited antitumor activity human cells. Mechanistically, YTHDC2, via m6A-recognizing YTH domain, cystine uptake and blocked downstream antioxidant program. Administration antioxidants to pulmonary YTHDC2-overexpressing mice rescued tumorigenesis. Furthermore, solute carrier 7A11 (SLC7A11), catalytic subunit system XC−, identified be direct target YTHDC2. destabilized SLC7A11 mRNA an m6A-dependent manner because preferentially bound m6A-modified thereafter promoted decay. Clinically, large proportion acinar subtype cases simultaneous downregulation elevation. Patient-derived xenograft (PDX) models generated from showed sensitivity XC− inhibitors. Collectively, promotion suppression critical for tumorigenesis, blocking this process may benefit future treatment.

Language: Английский

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Novel insights into the interplay between m6A modification and noncoding RNAs in cancer

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Aug. 7, 2020

N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes, mainly messenger (mRNA). Increasing evidence shows that m6A methylation modification acts an essential role various physiological and pathological bioprocesses. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs circRNAs, are known to participate regulating cell differentiation, angiogenesis, immune response, inflammatory response carcinogenesis. regulators, such as METTL3, ALKBH5 IGF2BP1 have been reported execute a m6A-dependent ncRNAs involved Meanwhile, can target or modulate regulators influence cancer development. In this review, we provide insight into interplay between cancer.

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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The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: Feb. 10, 2021

Abstract The human insulin-like growth factor 2 (IGF2) mRNA binding proteins (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type diabetes (T2D)-associated gene. Indeed modulates cellular metabolism in metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes cell types. Emerging evidence shows N6-methyladenosine (m6A) reader participates the development progression cancers by communicating with different RNAs microRNAs (miRNAs), messenger (mRNAs) long non-coding (lncRNAs). Additionally, independent prognostic for cancer In this review, we summarize current knowledge on regard diverse its potential prognosis.

Language: Английский

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The biological function of m6A demethylase ALKBH5 and its role in human disease

Cancer Cell International, Journal Year: 2020, Volume and Issue: 20(1)

Published: July 28, 2020

Abstract Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which dysregulated and acts as biological pharmacological role in human cancers or non-cancers. ALKBH5 plays dual various through regulating kinds of processes, such proliferation, migration, invasion, metastasis tumor growth. In addition, it takes great part non-cancer, including reproductive system diseases. The underlying regulatory mechanisms that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy hypoxia. also an independent prognostic indicator cancers. this review, we summarized the current evidence diverse non-cancers its potential target.

Language: Английский

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Role of m6A writers, erasers and readers in cancer

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Aug. 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.

Language: Английский

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RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential

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

Published: Jan. 21, 2022

RNA demethylase ALKBH5 takes part in the modulation of N

Language: Английский

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