DirectRMDB: a database of post-transcriptional RNA modifications unveiled from direct RNA sequencing technology DOI Creative Commons
Yuxin Zhang, Jie Jiang,

Jiongming Ma

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D106 - D116

Published: Nov. 16, 2022

Abstract With advanced technologies to map RNA modifications, our understanding of them has been revolutionized, and they are seen be far more widespread important than previously thought. Current next-generation sequencing (NGS)-based modification profiling methods blind modifications thus require selective chemical treatment or antibody immunoprecipitation for particular types. They also face the problem short read length, isoform ambiguities, biases artifacts. Direct (DRS) technologies, commercialized by Oxford Nanopore Technologies (ONT), enable direct interrogation any given present in individual transcripts promise address limitations previous NGS-based methods. Here, we first ONT-based database quantitative profiles, DirectRMDB, which includes 16 types a total 904,712 sites 25 species identified from 39 independent studies. In addition standard functions adopted existing databases, such as gene annotations post-transcriptional association analysis, provide fresh view enables exploration epitranscriptome an isoform-specific manner. The DirectRMDB is freely available at: http://www.rnamd.org/directRMDB/.

Language: Английский

RNA modifications: importance in immune cell biology and related diseases DOI Creative Commons
Lian Cui, Rui Ma,

Jiangluyi Cai

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

Citations

205
Regulation and functions of non-m6A mRNA modifications DOI

Hanxiao Sun,

Kai Li,

Cong Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(10), P. 714 - 731

Published: June 27, 2023

Language: Английский

Citations

136
Role of main RNA modifications in cancer: N6-methyladenosine, 5-methylcytosine, and pseudouridine DOI Creative Commons
Chen Xue,

Qingfei Chu,

Qiuxian Zheng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 28, 2022

Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in genetic material without any nucleic acid sequence results phenotypic changes. modifications regulate many biological processes, such as growth, aging, various diseases, including cancer. With advancement next-generation sequencing technology, role RNA cancer progression has become increasingly prominent a hot spot scientific research. This review studied several common modifications, N6-methyladenosine, 5-methylcytosine, pseudouridine. The deposition roles these coding noncoding RNAs are summarized detail. Based on background, this expression, function, underlying molecular mechanism their regulators further discussed some existing small-molecule inhibitors. More in-depth studies needed broaden understanding epigenetics diagnosis, treatment, prognosis.

Language: Английский

Citations

122
Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: impacts on therapeutic resistance DOI Creative Commons
Hong Lin, Di Wang, Pinghan Wang

et al.

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

Published: July 18, 2022

Abstract The resistance of tumor cells to therapy severely impairs the efficacy treatment, leading recurrence and metastasis various cancers. Clarifying underlying mechanisms therapeutic may provide new strategies for overcoming cancer resistance. N6-methyladenosine (m6A) is most prevalent RNA modification in eukaryotes, involved regulation splicing, translation, transport, degradation, stability processing, thus affecting several physiological processes progression. As a novel type multifunctional non-coding RNAs (ncRNAs), circular (circRNAs) have been demonstrated play vital roles anticancer therapy. Currently, accumulating studies revealed mutual m6A circRNAs, their interaction can further influence sensitivity treatment. In this review, we mainly summarized recent advances circRNAs modulation resistance, as well interplay potential mechanisms, providing promising insights future directions reversal cancer.

Language: Английский

Citations

84
Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA DOI Creative Commons

Chi Jin,

Tuo Wang, Dongsheng Zhang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Dec. 15, 2022

N

Language: Английский

Citations

84
Genetic and epigenetic defects of the RNA modification machinery in cancer DOI Creative Commons
Ines Oršolić,

Arnaud Carrier,

Manel Esteller

et al.

Trends in Genetics, Journal Year: 2022, Volume and Issue: 39(1), P. 74 - 88

Published: Nov. 12, 2022

Cancer was initially considered to be an exclusively genetic disease, but interplay of dysregulated and epigenetic mechanisms is now known contribute the cancer phenotype. More recently, chemical modifications RNA molecules - so-called epitranscriptome have been found regulate various aspects function homeostasis. Specific enzymes, as RNA-modifying proteins (RMPs), are responsible for depositing, removing, reading in RNA. Intensive investigations epitranscriptomic field recent years, conjunction with great technological advances, revealed critical role regulating numerous cellular pathways. Furthermore, growing evidence has that modification machinery often altered human cancers, highlighting enormous potential RMPs pharmacological targets or diagnostic markers.

Language: Английский

Citations

80
Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas DOI Creative Commons

Cheng Wei,

Bo Wang,

Dazhao Peng

et al.

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

Published: April 4, 2022

Background AlkB homolog 5 (ALKBH5) is a N 6 -methyladenosine (m A) demethylase associated with the development, growth, and progression of multiple cancer types. However, biological role ALKBH5 has not been investigated in pan-cancer datasets. Therefore, this study, comprehensive bioinformatics analysis datasets was performed to determine mechanisms through which regulates tumorigenesis. Methods Online websites databases such as NCBI, UCSC, CCLE, HPA, TIMER2, GEPIA2, cBioPortal, UALCAN, STRING, SangerBox, ImmuCellAl, xCell, GenePattern were used extract data cancers. The patient analyzed relationship between expression, genetic alterations, methylation status, tumor immunity. Targetscan, miRWalk, miRDB, miRabel, LncBase Cytoscape tool identify microRNAs (miRNAs) long non-coding RNAs (lncRNAs) that regulate expression construct lncRNA-miRNA-ALKBH5 network. In vitro CCK-8, wound healing, Transwell M2 macrophage infiltration assays well vivo xenograft animal experiments functions glioma cells. Results showed upregulated several solid tumors. significantly correlated prognosis patients. Genetic alterations including duplications deep mutations gene identified Alterations prognosis. GO KEGG enrichment analyses ALKBH5-related genes enriched inflammatory, metabolic, immune signaling pathways glioma. checkpoint (ICP) genes, influenced sensitivity immunotherapy. We constructed lncRNA-miRNA network development progression. promoted proliferation, migration, invasion cells recruited Conclusions overexpressed types cancers regulation tumor-infiltration Our study shows promising prognostic immunotherapeutic biomarker some malignant

Language: Английский

Citations

79
RNA modifications in cancer DOI

Qiling Tang,

Lvyuan Li,

Yumin Wang

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(2), P. 204 - 221

Published: April 24, 2023

Language: Английский

Citations

68
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
Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges DOI Creative Commons
Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Snur Rasool Abdullah

et al.

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: July 17, 2023

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of sciences during the last decade. In study cancer, CRISPR/CRISPR-associated protein (Cas) system opens avenues into issues that were once unknown in our knowledge noncoding genome, tumor heterogeneity, precision medicines. CRISPR/Cas-based gene-editing technology now allows for precise permanent targeting mutations provides an opportunity target small non-coding RNAs such as microRNAs (miRNAs). However, development effective safe cancer gene editing therapy is highly dependent on proper design be innocuous normal cells prevent introducing other abnormalities. This aims highlight cutting-edge approaches cancer-gene based CRISPR/Cas miRNAs therapy. Furthermore, we potential challenges CRISPR/Cas-mediated miRNA offer advanced strategies overcome them.

Language: Английский

Citations

59