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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m⁶A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2‐mediated IGF1R mRNA stabilization

Clinical and Translational Medicine, Journal Year: 2021, Volume and Issue: 11(6)

Published: June 1, 2021

Abstract Background Bone metastasis is the leading cause of tumor‐related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved progression multiple cancers. Nevertheless, role lncRNAs PCa bone remains largely unclear. Methods The expression cancer‐associated transcripts was analyzed published datasets and further verified clinical samples cell lines by RT‐qPCR situ hybridization assays. Colony formation assay, MTT cycle analysis, EdU Transwell migration invasion assays, wound healing vivo experiments were carried out investigate function transcript 6 ( PCAT6 ) tumor growth PCa. Bioinformatic RNA pull‐down, RIP assays conducted identify proteins binding potential targets . therapeutic targeting antisense oligonucleotides (ASO) explored Results upregulated tissues with increased predicted poor prognosis Functional found that knockdown significantly inhibited invasion, migration, proliferation vitro , as Mechanistically, METTL3 ‐mediated m A modification contributed upregulation an IGF2BP2 ‐dependent manner. Furthermore, IGF1R enhancing mRNA stability through / RNA‐protein three‐dimensional complex. Importantly, inhibition ASO showed against Finally, correlation demonstrated cells. Conclusions Our study uncovers a novel molecular mechanism which A‐induced axis promotes growth, suggesting may serve promising prognostic marker target bone‐metastatic

Language: Английский

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Oncofetal protein IGF2BPs in human cancer: functions, mechanisms and therapeutic potential

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: June 6, 2023

N6-methyladenosine (m6A) is the most prevalent and well-characterized internal chemical modification in eukaryotic RNA, influencing gene expression phenotypic changes by controlling RNA fate. Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) preferentially function as m6A effector proteins, promoting stability translation of m6A-modified RNAs. IGF2BPs, particularly IGF2BP1 IGF2BP3, are widely recognized oncofetal predominantly expressed cancer rather than normal tissues, playing a critical role tumor initiation progression. Consequently, IGF2BPs hold potential for clinical applications serve good choice targeted treatment strategies. In this review, we discuss functions mechanisms readers explore therapeutic targeting human cancer.

Language: Английский

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(7), P. 2744 - 2758

Published: Jan. 1, 2022

RNA can be modified by over 170 types of distinct chemical modifications, and the most abundant internal modification mRNA in eukaryotes is N6-methyladenosine (m

Language: Английский

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IGF2BPs as novel m6A readers: Diverse roles in regulating cancer cell biological functions, hypoxia adaptation, metabolism, and immunosuppressive tumor microenvironment

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(2), P. 890 - 920

Published: July 20, 2023

m6A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role cancer progression by regulating biological functions. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP) are newly identified 'readers'. They belong to family RNA-binding proteins, which bind sites on different RNA sequences stabilize them promote progression. In this review, we summarize mechanisms upstream factors regulate IGF2BP cancer. The current literature analyzed here reveals that cell proliferation, survival, chemoresistance, inhibit apoptosis, also associated with glycolysis, angiogenesis, immune response tumor microenvironment. Therefore, discovery their as 'readers' characteristic re-expression IGF2BPs cancers, it important elucidate mechanism action immunosuppressive We describe detail regulatory interaction network downstream target RNAs discuss potential clinical applications diagnostic prognostic markers, well recent advances biology therapeutic value.

Language: Английский

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Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106775 - 106775

Published: April 17, 2023

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of promotes carcinogenesis, increased proliferation, invasion, therapy resistance. As an incurable disease globally, prostate cancer significant health concern, research into genetic mutations function has efficacy facilitate introduction novel therapies. upregulation observed during progression, resulting cell cycle progression proliferation rates. Additionally, endorses resistance death enhances capacity for metastasis, particularly bone metastasis. Overexpression triggers chemoresistance radio-resistance, inhibition by anti-tumor compounds can reduce progression. Interestingly, non-coding RNA transcripts regulate level its nuclear transfer, offering potential avenue modulating

Language: Английский

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m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216735 - 216735

Published: Feb. 16, 2024

Language: Английский

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Emerging role of RNA modification and long noncoding RNA interaction in cancer

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(6), P. 816 - 830

Published: Feb. 14, 2024

Abstract RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence progression of cancer through multiple pathways. The function expression these epigenetic regulators have gradually become a hot topic research. Mutation regulation noncoding RNA, lncRNA, play major role cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions its dysregulation can promote tumor metastasis. In this review, we summarize modifications lncRNAs. Furthermore, discuss relationship between modification lncRNA interaction various cancers. Therefore, review gives comprehensive understanding mechanisms by which affects cancers regulating lncRNAs, may shed new light on research provide insights into therapy.

Language: Английский

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FBW7/GSK3β mediated degradation of IGF2BP2 inhibits IGF2BP2-SLC7A5 positive feedback loop and radioresistance in lung cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Jan. 29, 2024

Abstract Background The development of radioresistance seriously hinders the efficacy radiotherapy in lung cancer. However, underlying mechanisms by which occurs are still incompletely understood. N 6 -Methyladenosine (m A) modification RNA is involved cancer progression, but its role remains elusive. This study aimed to identify m A regulators radiosensitivity and further explore therapeutic targets overcome radioresistance. Methods Bioinformatic mining was used regulator IGF2BP2 radiosensitivity. Transcriptome sequencing downstream factors. Clonogenic survival assays, neutral comet Rad51 foci formation Annexin V/propidium iodide assays were determine significance FBW7/IGF2BP2/SLC7A5 axis Chromatin immunoprecipitation (ChIP)-qPCR analyses, (RIP) methylated (MeRIP)-qPCR pull-down co-immunoprecipitation ubiquitination feedback loop between SLC7A5 regulatory effect FBW7/GSK3β on IGF2BP2. Mice models tissue microarrays verify effects vivo. Results We identified IGF2BP2, an “reader”, that overexpressed facilitates showed inhibition impairs both vitro Furthermore, we found enhances stability translation mRNA through modification, resulting enhanced SLC7A5-mediated transport methionine produce S-adenosylmethionine. feeds back upon promoter region increasing trimethyl at lysine 4 histone H3 (H3K4me3) level upregulate expression. demonstrated this positive promotes AKT/mTOR pathway. Moreover, ubiquitin ligase FBW7 functions with GSK3β kinase recognize degrade Conclusions Collectively, our revealed “reader” forming a SLC7A5, suggesting may be potential target control

Language: Английский

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ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(16), P. 6145 - 6162

Published: Jan. 1, 2022

Background: N6-methyladenosine (m6A) is one of the most prevalent mRNA modifications in mammals, and it regulates fate modified RNA transcripts.In current study, we aimed to elucidate role YTH m6A RNA-binding protein 1 (YTHDF1), a "reader" modification, prostate cancer tumorigenesis.Methods: We employed multi-omics approach detect direct target YTHDF1 upon manipulation expression cells.Expression was also evaluated human tumors either adjacent or paired normal tissues.Additionally, vivo tumor growth metastasis experimental assays were performed evaluate tumorigenesis.Finally, luciferase reporter Chromatin immunoprecipitation (ChIP) conducted transcriptional regulators YTHDF1.Results: demonstrated that polo-like kinase (PLK1) YTHDF1.YTHDF1 facilitated translation efficiency PLK1 an m6A-dependent manner by identifying m6A-modified subsequently promoted hyperactivation PI3K/AKT signaling pathway.Moreover, our results indicated upregulated tissue high associated with adverse prognosis patients cancer.Furthermore, upregulation tumorigenesis vitro vivo.Additionally, dysregulation ETS transcription factor ELK1 activated directly binding its promoter region.Conclusions: Collectively, findings suggest ELK1/YTHDF1/PLK1/PI3K/AKT axis critical for progression may serve as potential therapeutic treatment.

Language: Английский

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