Towards a druggable epitranscriptome: Compounds that target RNA modifications in cancer

被引：25

作者：

Berdasco, Maria ^{[1
,2
]}

Esteller, Manel ^{[3
,4
,5
,6
]}

机构：

[1] Josep Carreras Leukaemia Res Inst, Epigenet Therapies Grp, Expt & Clin Hematol Program PHEC, Barcelona, Catalonia, Spain

[2] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona, Spain

[3] Josep Carreras Leukaemia Res Inst IJC, Canc Epigenet Grp, Canc & Leukemia Epigenet & Biol Program PEBCL, Barcelona, Catalonia, Spain

[4] Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain

[5] Univ Barcelona, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona, Spain

[6] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2022年 / 179卷 / 12期

关键词：

A-to-I-editing; cancer; epitranscriptomics; pseudouridine; RNA methylation; small-molecule inhibitors; therapy; MESSENGER-RNA; CONCISE GUIDE; GENE-EXPRESSION; ADENOSINE-DEAMINASE; MYELOID-LEUKEMIA; NONCODING RNAS; SELF-RENEWAL; NUCLEAR-RNA; M(6)A; PROTEIN;

D O I：

10.1111/bph.15604

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Epitranscriptomics is an exciting emerging area that studies biochemical modifications of RNA. The field has been opened up by the technical efforts of the last decade to characterize and quantify RNA modifications, and this has led to a map of post-transcriptional RNA marks in normal cell fate and development. However, the scientific interest has been fuelled by the discovery of aberrant epitranscriptomes associated with human diseases, mainly cancer. The challenge is now to see whether epitrancriptomics offers mechanisms that can be effectively targeted by low MW compounds and are thus druggable. In this review, we will describe the principal RNA modifications (with a focus on mRNA), summarize the latest scientific evidence of their dysregulation in cancer and provide an overview of the state-of-the-art drug discovery to target the epitranscriptome. Finally, we will discuss the principal challenges in the field of chemical biology and drug development to increase the potential of targeted-RNA for clinical benefit.

引用

页码：2868 / 2889

页数：22

共 156 条

[1] HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events [J].

Alarcon, Claudio R. ;

Goodarzi, Hani ;

Lee, Hyeseung ;

Liu, Xuhang ;

Tavazoie, Saeed ;

Tavazoie, Sohail F. .

CELL, 2015, 162 (06) :1299-1308

[2] N6-methyladenosine marks primary microRNAs for processing [J].

Alarcon, Claudio R. ;

Lee, Hyeseung ;

Goodarzi, Hani ;

Halberg, Nils ;

Tavazoie, Sohail F. .

NATURE, 2015, 519 (7544) :482-+

[3] THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Catalytic receptors [J].

Alexander, Stephen P. H. ;

Fabbro, Doriano ;

Kelly, Eamonn ;

Mathie, Alistair ;

Peters, John A. ;

Veale, Emma L. ;

Armstrong, Jane F. ;

Faccenda, Elena ;

Harding, Simon D. ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Davies, Jamie A. .

BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 :S247-S296

[4]

Alexander SPH, 2019, BRIT J PHARMACOL, V176, pS297, DOI [10.1111/bph.14752, 10.1111/bph.14749]

[5] THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors [J].

Alexander, Stephen P. H. ;

Christopoulos, Arthur ;

Davenport, Anthony P. ;

Kelly, Eamonn ;

Mathie, Alistair ;

Peters, John A. ;

Veale, Emma L. ;

Armstrong, Jane F. ;

Faccenda, Elena ;

Harding, Simon D. ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Davies, Jamie A. ;

Arumugam, Thiruma V. ;

Bennett, Andrew ;

Sjogren, Benita ;

Sobey, Christopher ;

Wong, Szu Shen ;

Abbracchio, Maria P. ;

Alexander, Wayne ;

Al-hosaini, Khaled ;

Back, Magnus ;

Beaulieu, Jean-Martin ;

Bernstein, Kenneth E. ;

Bettler, Bernhard ;

Birdsall, Nigel J. M. ;

Blaho, Victoria ;

Bousquet, Corinne ;

Brauner-Osborne, Hans ;

Burnstock, Geoffrey ;

Calo, Girolamo ;

Castano, Justo P. ;

Catt, Kevin J. ;

Ceruti, Stefania ;

Chazot, Paul ;

Chiang, Nan ;

Chun, Jerold ;

Cianciulli, Antonia ;

Clapp, Lucie H. ;

Couture, Rejean ;

Csaba, Zsolt ;

Dent, Gordon ;

Singh, Khuraijam Dhanachandra ;

Douglas, Steven D. ;

Dournaud, Pascal ;

Eguchi, Satoru ;

Escher, Emanuel ;

Filardo, Edward ;

Fong, Tung M. .

BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 :S21-S141

[6] THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors [J].

Alexander, Stephen P. H. ;

Cidlowski, John A. ;

Kelly, Eamonn ;

Mathie, Alistair ;

Peters, John A. ;

Veale, Emma L. ;

Armstrong, Jane F. ;

Faccenda, Elena ;

Harding, Simon D. ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Davies, Jamie A. .

BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 :S229-S246

[7] THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets [J].

Alexander, Stephen P. H. ;

Kelly, Eamonn ;

Mathie, Alistair ;

Peters, John A. ;

Veale, Emma L. ;

Armstrong, Jane F. ;

Faccenda, Elena ;

Harding, Simon D. ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Buneman, O. Peter ;

Cidlowski, John A. ;

Christopoulos, Arthur ;

Davenport, Anthony P. ;

Fabbro, Doriano ;

Spedding, Michael ;

Striessnig, Joerg ;

Davies, Jamie A. .

BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 :S1-S20

[8] The molecular hallmarks of epigenetic control [J].

Allis, C. David ;

Jenuwein, Thomas .

NATURE REVIEWS GENETICS, 2016, 17 (08) :487-500

[9] Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis [J].

Anadon, C. ;

Guil, S. ;

Simo-Riudalbas, L. ;

Moutinho, C. ;

Setien, F. ;

Martinez-Cardus, A. ;

Moran, S. ;

Villanueva, A. ;

Calaf, M. ;

Vidal, A. ;

Lazo, P. A. ;

Zondervan, I. ;

Savola, S. ;

Kohno, T. ;

Yokota, J. ;

Ribas de Pouplana, L. ;

Esteller, M. .

ONCOGENE, 2016, 35 (33) :4407-4413

[10] New insights into the epigenetics of inflammatory rheumatic diseases [J].

Ballestar, Esteban ;

Li, Tianlu .

NATURE REVIEWS RHEUMATOLOGY, 2017, 13 (10) :593-605

← 1 2 3 4 5 6 7 8 9 10 →