Gene, Journal Year: 2025, Volume and Issue: 959, P. 149518 - 149518
Published: April 18, 2025
Language: Английский
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: Aug. 30, 2024
Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.
Language: Английский
Citations
18
Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)
Published: Feb. 21, 2025
Language: Английский
Citations
3
Biology Direct, Journal Year: 2023, Volume and Issue: 18(1)
Published: Sept. 14, 2023
Abstract M7G modification, known as one of the common post-transcriptional modifications RNA, is present in many different types RNAs. With accurate identification m7G within RNAs, their functional roles regulation gene expression and physiological functions have been revealed. In addition, there growing evidence that are crucial emergence cancer. Here, we review most recent findings regarding detection techniques, distribution, biological Regulators m7G. We also summarize connections between cancer development, drug resistance, tumor microenvironment well discuss research’s future directions trends.
Language: Английский
Citations
30
Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3417 - 3427
Published: Nov. 15, 2023
More than 170 different types of chemical modifications have been identified on diverse RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) ubiquitous post-transcriptional modification are widely involved in regulating metabolic processes such RNA degradation, translation, stability, export, mediating important physiological pathological stress regulation, immune response, development, tumorigenesis. Recently, regulatory role during developmental is getting more attention. Therefore, development low-input even single-cell high-resolution sequencing technologies crucial for exploration roles these biological events trace samples.This account focuses various processes. We describe distribution characteristics modifications, catalytic enzymes, binding proteins, technologies. dynamically reversible, which can be catalyzed by methyltransferases eliminated demethylases. m6A most abundant eukaryote mRNA, mainly concentrated near stop codon, involves metabolism regulation. m5C, another studied modification, has a organisms species, enriched regions downstream translation initiation sites broadly distributes across whole coding sequence (CDS) mammalian mRNAs. m1A, with lower abundance m6A, distributed types, locates 5' untranslated region (5'UTR) mRNA regulates translation. m7G, one common eukaryotes, at cap internal positions RNAs recently gained considerable attention.Thanks to technology, found regulate tumorigenic process, including tumor proliferation, invasion, metastasis modulating oncogenes suppressor genes, affect oocyte maturation embryonic through maternal zygotic genes. m5C related proteins participate plant growth, neural stem cell differentiation dependent manner. m1A also revealed m7G dysregulation neurodevelopmental disorders neurodegenerative diseases.Collectively, we summarized gradually exhibited methylation discussed possibility candidate biomarkers potential therapeutic targets. The technological anticipated major driving force expand our knowledge this field.
Language: Английский
Citations
28
Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)
Published: Aug. 21, 2023
N7-methylguanosine (m7G) modification is, a more common epigenetic in addition to m6A modification, mainly found mRNA capsids, interiors, transfer RNA (tRNA), pri-miRNA, and ribosomal (rRNA). It has been that m7G modifications play an important role transcription, tRNA stability, rRNA processing maturation, miRNA biosynthesis. However, the of within its "writer" methyltransferase 1(METTL1) tumors, particularly prostate cancer (PCa), not revealed.The differential expression level METTL1 between hormone-sensitive (HSPC) castrate-resistant (CRPC) was evaluated via RNA-seq vitro experiments. The effects on CRPC progression were investigated through vivo assays. upstream molecular mechanism upregulation downstream action explored Chromatin Immunoprecipitation quantitative reverse transcription polymerase chain reaction (CHIP-qPCR), Co-immunoprecipitation (Co-IP), luciferase reporter assay, transcriptome-sequencing, AlkAniline-Seq, degradation experiments, etc. RESULTS AND CONCLUSION: Here, we elevated patients with elevation tended have poor prognosis. Functionally, knockdown cells significantly limited cell proliferation invasive capacity. Mechanistically, unveiled P300 can form complex SP1 bind promoter region gene SP1, thereby mediating transcriptional CRPC. Subsequently, our findings indicated leads enhanced stability CDK14 by adding inside mRNA, ultimately promoting progression.
Language: Английский
Citations
23
Advanced Science, Journal Year: 2024, Volume and Issue: 11(29)
Published: May 29, 2024
Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1-catalyzed RNA N7-methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 mechanism underlying non-ischemic HF. It found that upregulated human failing hearts hypertrophic murine following transverse aortic constriction (TAC) Angiotensin II (Ang II) infusion. YY1 acts as transcriptional for during hypertrophy. knockout alleviates dysfunction upon pressure overload from TAC or Ang stimulation. Conversely, cardiac-specific overexpression results remodeling. Mechanically, increases SRSF9 expression by inducing m7G mRNA, facilitating alternative splicing stabilization NFATc4, thereby promoting Moreover, knockdown protects against TAC- Mettl1-induced phenotypes vivo vitro. The identifies crucial regulator hypertrophy, providing novel therapeutic target
Language: Английский
Citations
13
International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1238 - 1255
Published: Jan. 1, 2024
RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level.Among these modifications, N7-methylguanosine (m7G) stands out as one of most prevalent.Over recent years, significant attention has been directed towards understanding implications m7G modification.This modification is present diverse molecules, including transfer RNAs, messenger ribosomal other noncoding RNAs.Its regulation occurs through series specific methyltransferases m7G-binding proteins.Notably, implicated various diseases, prominently across multiple cancer types.Earlier studies have elucidated significance context immune within tumor microenvironment.This comprehensive review culminates synthesis findings related to modulation cells infiltration, encompassing T cells, B innate all orchestrated modification.Furthermore, interplay between its regulatory proteins can profoundly affect efficacy adjuvant therapeutics, thereby potentially serving biomarker therapeutic target for combinatory interventions types.
Language: Английский
Citations
10
Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Neurodegenerative diseases (NDs) constitute a significant public health challenge, as they are increasingly contributing to global mortality and morbidity, particularly among the elderly population. Pathogenesis of NDs is intricate multifactorial. Recently, post-transcriptional modifications (PTMs) RNA, with particular focus on mRNA methylation, have been gaining increasing attention. At present, several regulatory genes associated methylation identified closely neurodegenerative disorders. This review aimed summarize RNA enzymes system, including writer, reader, eraser proteins delve into their functions in central nervous system (CNS), hoping open new avenues for exploring mechanisms therapeutic strategies NDs. studies highlighted critical role development function CNS, abnormalities this process may contribute brain damage NDs, aberrant expression involved has implicated onset
Language: Английский
Citations
1
Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)
Published: Jan. 29, 2025
N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that commonly observed both prokaryotic and eukaryotic organisms. Their influence on the synthesis processing of messenger RNA, ribosomal transfer allows m7G modifications to affect diverse cellular, physiological, pathological processes. are pivotal human diseases, particularly cancer progression. On one hand, modification-associated modulate tumour progression malignant biological characteristics, including sustained proliferation signalling, resistance cell death, activation invasion metastasis, reprogramming energy metabolism, genome instability, immune evasion. This suggests they may be novel therapeutic targets for treatment. other aberrant expression molecules linked clinicopathological staging, lymph node unfavourable prognoses patients with cancer, indicating their potential as biomarkers. review consolidates discovery, identification, detection methodologies, functional roles modification, analysing mechanisms by which contribute development, exploring clinical applications diagnostics therapy, thereby providing innovative strategies identification targeted
Language: Английский
Citations
1
Molecular Carcinogenesis, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 17, 2025
ABSTRACT METTL1, a well‐established RNA methyltransferase for the N(7)‐methylguanosine (m7G) methylation modification, is responsible human tumorigenesis. Here, we aimed to examine activity and molecular determinants of METTL1 in colorectal cancer (CRC) development. ribosomal processing 9 (RRP9) mRNA analysis was performed by quantitative PCR. Protein expression detected immunoblotting immunohistochemistry (IHC). Cell sphere formation, invasion, proliferation were assessed transwell, MTT assays, respectively. migration tested transwell wound healing assays. Subcutaneous xenografts produced analyze role vivo. The influence m7G stability RRP9 evaluated methylated immunoprecipitation (MeRIP) assay Actinomycin D (Act D) treatment, highly expressed CRC tumors cell lines. depletion suppressed proliferation, invasiveness, migratory ability, formation potential vitro, while increased had opposite effects. positively correlated with CRC. Mechanistically, promoted mediating its methylation, regulated PI3K/AKT signaling RRP9. Increased partially reversed suppressive effects on phenotypes vitro. impeded growth HCT‐116 subcutaneous vivo Our observations identified as crucial protumorigenic factor drive growth, metastasis, stemness cells through RRP9, offering new targets combating
Language: Английский
Citations
1