The role of RNA modification in the generation of acquired drug resistance in glioma DOI Creative Commons
Yu Yan, Wei Wei, Shengrong Long

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 11, 2022

Glioma is the most common malignant tumor in central nervous system. The clinical treatment strategy mainly surgery combined with concurrent temozolomide chemotherapy, but patients can develop drug resistance during treatment, which severely limits its therapeutic efficacy. Epigenetic regulation at RNA level plastic and adaptable, it induce a variety of responses to drugs. regulators modification include methyltransferases, demethylases, methylation binding proteins; these are also considered play an important role development, prognosis, response gliomas, provides basis for finding new targets epigenetic drugs resetting sensitivity cells temozolomide. This review discusses relationship between development adaptive glioma summarizes progress several major strategies this field, especially m6A modification, m5C adenosine-to-inosine editing.

Language: Английский

RNA modification: mechanisms and therapeutic targets DOI Creative Commons
Lei Qiu, Jing Qian, Yanbo Li

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Aug. 24, 2023

Abstract RNA modifications are dynamic and reversible chemical on substrate that regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes various diseases, such as development cancer other diseases. With help advanced sequencing technologies, role has caught increasing attention human diseases scientific research. In this review, we briefly summarized basic mechanisms several common modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing ac4C. Importantly, discussed their potential functions cancer, neurological disorders, cardiovascular metabolic genetic developmental well immune disorders. Through “writing-erasing-reading” mechanisms, regulate stability, translation, localization pivotal disease-related mRNAs to manipulate disease development. Moreover, also highlighted review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most which designed against m6A-related enzymes, METTL3, FTO ALKBH5. This provides clues for clinical therapy future study directions modification field. More in-depth studies further activators needed a thorough understanding epitranscriptomics diagnosis, treatment, prognosis

Language: Английский

Citations

68
Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases DOI Creative Commons
Xiaohuan Xia, Yi Wang, Jialin Zheng

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2023, Volume and Issue: 31, P. 295 - 308

Published: Jan. 11, 2023

In recent years, N7-methylguanosine (m7G) methylation, originally considered as messenger RNA (mRNA) 5′ caps modifications, has been identified at defined internal positions within multiple types of RNAs, including transfer ribosomal miRNA, and mRNAs. Scientists have put substantial efforts to discover m7G methyltransferases methylated sites in RNAs unveil the essential roles modifications regulation gene expression determine association dysregulation various diseases, neurological disorders. Here, we review findings regarding distribution, abundance, biogenesis, modifiers, functions modifications. We also provide an up-to-date summary detection profile mapping techniques, databases for validated predicted sites, web servers methylation prediction. Furthermore, discuss pathological METTL1/WDR-driven Last, outline a roadmap future directions trends modification research, particularly central nervous system.

Language: Английский

Citations

45
The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer DOI Creative Commons
Vincenza Ylenia Cusenza, Annalisa Tameni, Antonino Neri

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 9, 2023

Most of our transcribed RNAs are represented by non-coding sequences. Long (lncRNAs) transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) 2’-O-methylation (Nm) some the lncRNAs epigenetic modifications. The modifications RNA controlled three classes enzymes, each playing role in specific phase modification. These enzymes defined as “writers”, “readers” “erasers”. m6A m5C most studied RNA. alter structure properties, thus modulating functions interactions lncRNAs. aberrant expression several is linked to development variety cancers signatures m6A- m5C-related increasingly recognized potential biomarkers prognosis, predictors disease stage overall survival. In present manuscript, up date literature reviewed focus on their significance cancer.

Language: Английский

Citations

43
New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication DOI Creative Commons
Sha Qin,

Bin Xie,

Qingyi Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(6)

Published: May 23, 2024

Abstract Cancer is one of the leading causes death worldwide, and more effective ways attacking cancer are being sought. immunotherapy a new therapeutic method after surgery, radiotherapy, chemotherapy, targeted therapy. aims to kill tumor cells by stimulating or rebuilding body's immune system, with specific efficiency high safety. However, only few patients respond due complex variable characters escape, behavior regulatory mechanisms need be deeply explored from dimensions. Epigenetic modifications, metabolic modulation, cell‐to‐cell communication key factors in cell adaptation response microenvironment. They collectively determine state function through modulating gene expression, changing energy nutrient demands. In addition, engage networks other components, which mediated exosomes, cytokines, chemokines, pivotal shaping progression response. Understanding interactions combined effects such multidimensions modulation important for revealing failure developing targets strategies.

Language: Английский

Citations

13
Molecular insights into regulatory RNAs in the cellular machinery DOI Creative Commons
Sumin Yang, Sung-Hyun Kim, Eun-Jeong Yang

et al.

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(6), P. 1235 - 1249

Published: June 14, 2024

It is apparent that various functional units within the cellular machinery are derived from RNAs. The evolution of sequencing techniques has resulted in significant insights into approaches for transcriptome studies. Organisms utilize RNA to govern systems, and a heterogeneous class RNAs involved regulatory functions. In particular, increasingly recognized participate intricately functioning across almost all levels biological systems. These systems include those mediating chromatin arrangement, transcription, suborganelle stabilization, posttranscriptional modifications. Any exhibiting activity can be termed typically represented by noncoding RNAs, which constitute substantial portion genome. function based on principle structural changes through cis and/or trans regulation facilitate mutual RNA‒RNA, RNA‒DNA, RNA‒protein interactions. not been clearly elucidated whether identified deep actually anticipated mechanisms. This review addresses dominant properties at layers covers activities, dynamics, modifications, associated molecules, further challenges related therapeutics learning.

Language: Английский

Citations

12
Epigenetic frontiers: miRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy DOI Creative Commons
Rajkumar Prabhakaran,

Rajkumar Thamarai,

Sivabalan Sivasamy

et al.

Epigenetics & Chromatin, Journal Year: 2024, Volume and Issue: 17(1)

Published: Oct. 16, 2024

Cancer has arisen from both genetic mutations and epigenetic changes, making epigenetics a crucial area of research for innovative cancer prevention treatment strategies. This dual perspective propelled into the forefront research. review highlights important roles DNA methylation, histone modifications non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) long RNAs, which are key regulators cancer-related gene expression. It explores potential epigenetic-based therapies to revolutionize patient outcomes by selectively modulating specific markers involved in tumorigenesis. The examines promising biomarkers early detection prognosis. also recent progress oligonucleotide-based therapies, including antisense oligonucleotides (ASOs) antimiRs, precisely modulate processes. Furthermore, concept editing is discussed, providing insight future role precision medicine patients. integration nanomedicine therapy been explored offers approaches improve therapeutic efficacy. comprehensive advances seeks advance field oncology, ultimately culminating improved fight against cancer.

Language: Английский

Citations

7
A methylation- and immune-related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance DOI Creative Commons

Lu Chen,

Wujiang Gao,

Lin Li

et al.

Journal of Ovarian Research, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 6, 2023

Abstract Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role regulating cell infiltration sensitizing OC to chemotherapy modulating immune-related (irlncRNAs), which represent tumor status. Through deep analysis of TCGA database, prognostic risk model incorporating four methylation-related (mrlncRNAs) irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified significantly related overall survival (OS) patients. Subsequently, selected construct signature predictive OS indicative infiltration, verified robustness an internal validation set. The score independent factor for prognosis, demonstrated via multifactorial Cox regression nomogram. Moreover, scores negatively expression CD274, CTLA4, ICOS, LAG3, PDCD1, PDCD1LG2 correlated with CD8 + , CD4 Treg tumor-infiltrating cells. In addition, high-risk associated higher IC50 value cisplatin, worse clinical outcome. Next, competing endogenous RNA (ceRNA) network signaling pathway controlling T cells explored based on lncRNA model, suggested potential therapeutic target immunotherapy. Overall, this study constructed pairing mrlncRNAs revealed critical FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 function enhancing anticancer therapy.

Language: Английский

Citations

13
Deciphering glioma epitranscriptome: focus on RNA modifications DOI
Christina Piperi,

Mariam Markouli,

Antonios N. Gargalionis

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(28), P. 2197 - 2206

Published: June 15, 2023

Language: Английский

Citations

12
Development, validation, and updating of prognostic models for m7G-associated genes in lower-grade gliomas (Preprint) DOI
Zaixiang Tang,

Lei Ao,

Jun Li

et al.

Published: Feb. 18, 2025

BACKGROUND Studies are aiming at developing prognostic models using N7-methylguanosine (m7G)-related genes in gliomas, however, with good predictive performance for lower-grade gliomas have yet to be developed. OBJECTIVE Based on m7G variants and clinical information, two prediction been derived predict the probability of survival patients TCGA. METHODS The were externally validated independent datasets. CGGA updated that created matched features local population. Two derived, updated. RESULTS Model 1, which was basis mRNA, only contains five genes: CD37, EIF3A, CALU, COLGALT1, DDX3X. 2 included six variables: grade, age, gender, IDH mutation status, 1p/19q codeletion status index model 1. C-statistic revised 1 0.764 (95%CI: 0.730-0.798) set 0.700 0.658- 0.742) test set. Regarding internal validation, 1000 bootstrap replications 0.848, while external 0.752 0.714-0.788). CONCLUSIONS Both exhibited satisfactory calibration after updating validation. models' web calculator is provided https://lhj0520.shinyapps.io/M7G-LGG_model/.

Language: Английский

Citations

0
RNA sequencing reveals differential long noncoding RNA expression profiles in bacterial and viral meningitis in children DOI Creative Commons
Xin Li,

Suzhen Sun,

Huifeng Zhang

et al.

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: Feb. 12, 2024

Abstract Background We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis children. Methods The peripheral blood five patients, samples, healthy individuals were collected for sequencing. Then, differentially expressed lncRNA mRNA detected vs. controls, patients. Besides, co-expression competing endogenous (ceRNA) networks constructed. Receiver operating characteristic curve (ROC) analysis was performed. Results Compared with control group, 2 lncRNAs 32 mRNAs identified 115 54 meningitis. meningitis, 165 765 31 specific 53 function enrichment results indicated that these involved innate immune response, inflammatory system process. A total 8 1401 relationships respectively found groups. ceRNA contained 1 lncRNA-mRNA pair 4 miRNA-mRNA pairs group. GPR68 KIF5C, analysis, had an area under (AUC) 1.00, while AUC OR52K2 CCR5 is 0.883 0.698, respectively. Conclusions Our research first profile children may provide new insight into understanding regulatory mechanisms.

Language: Английский

Citations

3