Experimental Cell Research, Journal Year: 2024, Volume and Issue: 442(1), P. 114190 - 114190
Published: Aug. 3, 2024
Language: Английский
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: June 20, 2024
Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.
Language: Английский
Citations
30
Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(5), P. 359 - 378
Published: Jan. 5, 2024
Language: Английский
Citations
24
Cell Research, Journal Year: 2024, Volume and Issue: 34(9), P. 609 - 629
Published: July 25, 2024
The advent of high-throughput sequencing uncovered that our genome is pervasively transcribed into RNAs are seemingly not translated proteins. It was also found non-coding RNA transcripts outnumber canonical protein-coding genes. This mindboggling discovery prompted a surge in research started unraveling the functional relevance these new genetic units, shaking classic definition "gene". While revolution still taking place, polysome/ribosome profiling and mass spectrometry analyses revealed peptides can be from non-canonical open reading frames. Therefore, it becoming evident coding vs dichotomy way blurrier than anticipated. In this review, we focus on several examples which binary classification genes outdated, since same bifunctional gene expresses both products. We discuss implications intricate usage terms molecular mechanisms expression biological outputs, often concordant, but surprisingly discordant. Finally, methodological caveats associated with study genes, highlight opportunities challenges therapeutic exploitation intricacy towards development anticancer therapies.
Language: Английский
Citations
20
Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)
Published: Aug. 17, 2024
tRNA-derived small RNAs (tsRNAs) are newly discovered non-coding RNA, which generated from tRNAs and reported to participate in several biological processes diseases, especially cancer; however, the mechanism of tsRNA involvement colorectal cancer (CRC) 5-fluorouracil (5-FU) is still unclear.
Language: Английский
Citations
15
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
Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)
Published: June 18, 2024
Abstract Emerging evidence indicates that transfer RNA (tRNA)‐derived small RNAs (tsRNAs), originated from tRNA with high abundance modifications, play an important role in many complex physiological and pathological processes. However, the biological functions regulatory mechanisms of modified tsRNAs cancer remain poorly understood. Here, it is screened for confirmed presence a novel m 7 G‐modified tsRNA, G‐3′‐tiRNA Lys TTT (mtiRL), variety chemical carcinogenesis models by combining sequencing G RNA‐modified chip. Moreover, found mtiRL, catalyzed G‐modifying enzyme mettl1, promotes bladder (BC) malignancy vitro vivo. Mechanistically, mtiRL to specifically bind oncoprotein Annexin A2 (ANXA2) promote its Tyr24 phosphorylation enhancing interactions between ANXA2 Yes proto‐oncogene 1 (Yes1), leading activation increased p‐ANXA2‐Y24 nuclear localization BC cells. Together, these findings define critical suggest targeting this tsRNA can be efficient way treat BC.
Language: Английский
Citations
10
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
9
NAR Cancer, Journal Year: 2024, Volume and Issue: 6(1)
Published: Jan. 9, 2024
Abstract Recent advancements have illuminated the critical role of RNA modifications in post-transcriptional regulation, shaping landscape gene expression. This review explores how tRNA emerge as players, fine-tuning functionalities that not only maintain fidelity protein synthesis but also dictate expression and translation profiles. Highlighting their dysregulation a common denominator various cancers, we systematically investigate intersection both cytosolic mitochondrial with cancer biology. These impact key processes such cell proliferation, tumorigenesis, migration, metastasis, bioenergetics modulation tumor immune microenvironment. The recurrence altered modification patterns across different types underscores significance development, proposing them potential biomarkers actionable targets to disrupt tumorigenic processes, offering new avenues for precision medicine battle against cancer.
Language: Английский
Citations
9
Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)
Published: May 31, 2024
RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that related to various disease processes, including malignant tumors. However, the biological functions methyltransferase-like 1 (METTL1)-regulated m7G in breast cancer (BC) remain largely obscure. The role METTL1 BC progression were examined by cellular loss- and gain-of-function tests xenograft models both vitro vivo. To investigate change modification mRNA translation efficiency BC, m7G-methylated immunoprecipitation sequencing (m7G MeRIP-seq), Ribosome profiling (Ribo-seq), polysome-associated performed. Rescue assays conducted decipher underlying molecular mechanisms. methyltransferase complex components WD repeat domain 4 (WDR4) down-regulated tissues at protein levels. Functionally, inhibited cell proliferation, cycle progression, relying on its enzymatic activity. Mechanistically, increased levels 19 tRNAs modulate growth arrest DNA damage 45 alpha (GADD45A) retinoblastoma (RB1) a codon-dependent manner associated with m7G. Furthermore, vivo experiments showed overexpression enhanced anti-tumor effectiveness abemaciclib, cyclin-dependent kinases 6 (CDK4/6) inhibitor. Our study uncovered crucial tumor-suppressive METTL1-mediated promoting GADD45A RB1 mRNAs, selectively blocking G2/M phase cycle. These findings also provided promising strategy improving therapeutic benefits CDK4/6 inhibitors treatment patients.
Language: Английский
Citations
9
MedComm, Journal Year: 2025, Volume and Issue: 6(1)
Published: Jan. 1, 2025
Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.
Language: Английский
Citations
1