Pan-cancer characterization of long non-coding RNA and DNA methylation mediated transcriptional dysregulation.

Computational Biology / methods DNA Copy Number Variations DNA Methylation Databases, Genetic Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Humans Neoplasms / genetics Prognosis RNA, Long Noncoding / genetics Sequence Analysis, RNA
DNA methylation LncRNA Omics-data integration Regulatory network Transcriptional regulation

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Jun 2021
Historique:
received: 01 04 2021
revised: 29 04 2021
accepted: 29 04 2021
pubmed: 28 5 2021
medline: 15 12 2021
entrez: 27 5 2021
Statut: ppublish

Résumé

Disruption of DNA methylation (DNAm) is one of the key signatures of cancer, however, detailed mechanisms that alter the DNA methylome in cancer remain to be elucidated. Here we present a novel integrative analysis framework, called MeLncTRN (Methylation mediated LncRNA Transcriptional Regulatory Network), that integrates genome-wide transcriptome, DNA methylome and copy number variation profiles, to systematically identify the epigenetically-driven lncRNA-gene regulation circuits across 18 cancer types. We show that a significant fraction of the aberrant DNAm and gene expression landscape in cancer is associated with long noncoding RNAs (lncRNAs). We reveal distinct types of regulation between lncRNA modulators and target genes that are operative in either only specific cancers or across cancers. Functional studies identified a common theme of cancer hallmarks that lncRNA modulators may participate in. The coupled lncRNA gene interactions via DNAm also serve as markers for classifications of cancer subtypes with different prognoses. Our study reveals a vital layer of DNAm and associated expression regulation for many cancer-related genes and we also provide a valuable database resource for interrogating epigenetically mediated lncRNA-gene interactions in cancer. National Natural Science Foundation of China [91959106, 31871255].

Sections du résumé

BACKGROUND BACKGROUND
Disruption of DNA methylation (DNAm) is one of the key signatures of cancer, however, detailed mechanisms that alter the DNA methylome in cancer remain to be elucidated.
METHODS METHODS
Here we present a novel integrative analysis framework, called MeLncTRN (Methylation mediated LncRNA Transcriptional Regulatory Network), that integrates genome-wide transcriptome, DNA methylome and copy number variation profiles, to systematically identify the epigenetically-driven lncRNA-gene regulation circuits across 18 cancer types.
FINDING RESULTS
We show that a significant fraction of the aberrant DNAm and gene expression landscape in cancer is associated with long noncoding RNAs (lncRNAs). We reveal distinct types of regulation between lncRNA modulators and target genes that are operative in either only specific cancers or across cancers. Functional studies identified a common theme of cancer hallmarks that lncRNA modulators may participate in. The coupled lncRNA gene interactions via DNAm also serve as markers for classifications of cancer subtypes with different prognoses.
INTERPRETATION CONCLUSIONS
Our study reveals a vital layer of DNAm and associated expression regulation for many cancer-related genes and we also provide a valuable database resource for interrogating epigenetically mediated lncRNA-gene interactions in cancer.
FUNDING BACKGROUND
National Natural Science Foundation of China [91959106, 31871255].

Identifiants

DOI: 10.1016/j.ebiom.2021.103399 PMID: 34044218 PMC: PMC8245911
pubmed: 34044218
pii: S2352-3964(21)00192-4
doi: 10.1016/j.ebiom.2021.103399
pmc: PMC8245911
pii:
doi:

Substances chimiques

RNA, Long Noncoding 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103399

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no competing financial interests.

Références

Asian Pac J Cancer Prev. 2016;17(9):4217-4222
pubmed: 27797221
Nat Commun. 2015 Dec 21;6:10221
pubmed: 26687445
Genome Biol. 2015 Jul 14;16:140
pubmed: 26169266
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
Nucleic Acids Res. 2019 Jan 8;47(D1):D1034-D1037
pubmed: 30285109
Bioinformatics. 2014 Aug 15;30(16):2360-6
pubmed: 24794928
Bioinformatics. 2001 Jun;17(6):520-5
pubmed: 11395428
Nucleic Acids Res. 2018 Jan 4;46(D1):D371-D374
pubmed: 29106639
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Cell. 2014 Aug 14;158(4):929-944
pubmed: 25109877
Cell Rep. 2019 Mar 19;26(12):3461-3474.e5
pubmed: 30893615
Elife. 2013 Sep 03;2:e00726
pubmed: 24015356
BMC Biol. 2013 May 30;11:59
pubmed: 23721193
Cell. 2012 Jul 6;150(1):12-27
pubmed: 22770212
Oncol Rep. 2017 Jan;37(1):3-9
pubmed: 27841002
Nat Rev Genet. 2016 May;17(5):284-99
pubmed: 26972587
Transcription. 2019 Aug - Oct;10(4-5):171-186
pubmed: 31791217
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11667-72
pubmed: 19571010
Essays Biochem. 2019 Dec 20;63(6):707-715
pubmed: 31551326
Acta Biochim Biophys Sin (Shanghai). 2017 Jul 1;49(7):588-597
pubmed: 28645161
J Cell Physiol. 2019 Feb;234(2):1346-1353
pubmed: 30076714
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Genome Biol. 2011;12(4):R41
pubmed: 21527027
Nucleic Acids Res. 2018 Feb 16;46(3):1113-1123
pubmed: 29325141
Trends Cell Biol. 2010 Oct;20(10):609-17
pubmed: 20810283
Cancer Med. 2016 Dec;5(12):3512-3519
pubmed: 27794184
Cancer Cell Int. 2019 Apr 29;19:114
pubmed: 31168296
Nat Rev Genet. 2004 Feb;5(2):101-13
pubmed: 14735121
Commun Biol. 2020 Feb 5;3(1):56
pubmed: 32024996
Genome Res. 2005 Aug;15(8):1034-50
pubmed: 16024819
Mol Cell. 2014 Jun 5;54(5):766-76
pubmed: 24793693
Int J Biol Macromol. 2018 Sep;116:545-551
pubmed: 29753015
Nat Biotechnol. 2010 Oct;28(10):1057-68
pubmed: 20944598
Curr Opin Genet Dev. 1993 Apr;3(2):226-31
pubmed: 8504247
Mol Cell. 2014 Aug 21;55(4):604-14
pubmed: 25087872
Oncotarget. 2017 Sep 18;8(56):95542-95553
pubmed: 29221147
Cell Death Dis. 2020 Aug 11;11(8):676
pubmed: 32826865
Mol Ther Nucleic Acids. 2016 Nov 15;5(11):e385
pubmed: 27845772
Am J Physiol Gastrointest Liver Physiol. 2019 Aug 1;317(2):G222-G232
pubmed: 31125260
J Cell Physiol. 2018 Nov;233(11):8896-8907
pubmed: 29870057
Oncol Res. 2018 Aug 23;26(7):1083-1091
pubmed: 29321088
J Biol Chem. 2013 Nov 29;288(48):34287-94
pubmed: 24151070
Mol Ther. 2018 Sep 5;26(9):2267-2281
pubmed: 30037656
Gen Physiol Biophys. 2017 Dec;36(5):521-529
pubmed: 29372685
Nat Genet. 2013 Jun;45(6):632-8
pubmed: 23644492
Nature. 2006 Feb 16;439(7078):871-4
pubmed: 16357870
Cell Physiol Biochem. 2017;42(6):2453-2466
pubmed: 28848163
Nat Struct Mol Biol. 2013 Jul;20(7):908-13
pubmed: 23728290
Cell Prolif. 2017 Dec;50(6):
pubmed: 28940804
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
BMC Res Notes. 2020 Feb 21;13(1):88
pubmed: 32085812
Bioinformatics. 2005 Mar 1;21(5):650-9
pubmed: 15388519
Mol Carcinog. 2020 Jan;59(1):32-44
pubmed: 31621118
Nature. 2015 Nov 12;527(7577):249-53
pubmed: 26503055
Cell. 2011 Aug 5;146(3):353-8
pubmed: 21802130
Mol Cell. 2014 Jul 17;55(2):171-85
pubmed: 24882207
Mol Ther. 2017 Apr 5;25(4):1014-1026
pubmed: 28214253
Genome Res. 2012 Sep;22(9):1760-74
pubmed: 22955987
Cell Death Dis. 2017 Dec 7;8(12):e3175
pubmed: 29215608
Chemosphere. 2018 Sep;207:84-90
pubmed: 29772428
Nature. 2012 Feb 15;483(7390):479-83
pubmed: 22343889
Biomed Pharmacother. 2017 Dec;96:299-304
pubmed: 28992472
Nucleic Acids Res. 2019 Jan 8;47(D1):D853-D858
pubmed: 30407534
Development. 2013 Mar;140(6):1184-95
pubmed: 23444351
Cell. 2013 Mar 28;153(1):38-55
pubmed: 23540689
Bioinformatics. 2011 Jun 1;27(11):1496-505
pubmed: 21471010
Cell. 2018 Jan 25;172(3):393-407
pubmed: 29373828
Nature. 2013 Nov 21;503(7476):371-6
pubmed: 24107992
Biosci Rep. 2018 Oct 2;38(5):
pubmed: 29967294
Oncol Rep. 2020 Feb;43(2):718-726
pubmed: 31894346
Nat Genet. 2015 Mar;47(3):199-208
pubmed: 25599403
PLoS One. 2011;6(11):e27720
pubmed: 22110740
PLoS Med. 2013 Nov;10(11):e1001551
pubmed: 24265601
J Cancer. 2018 Oct 18;9(22):4156-4165
pubmed: 30519315
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
Cancer Cell. 2015 Oct 12;28(4):529-540
pubmed: 26461095
Mol Cancer. 2015 Sep 04;14:165
pubmed: 26336870
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Nat Rev Genet. 2012 May 29;13(7):484-92
pubmed: 22641018
PLoS One. 2007 Nov 14;2(11):e1182
pubmed: 18000552
Neoplasma. 2020 Mar;67(2):410-414
pubmed: 31884802
Sci Rep. 2016 Sep 15;6:33535
pubmed: 27628540
Mol Cell. 2016 Nov 3;64(3):565-579
pubmed: 27871486
Semin Cancer Biol. 2015 Feb;30:4-12
pubmed: 24747696
Genetics. 2013 Mar;193(3):651-69
pubmed: 23463798
Nat Genet. 2010 Dec;42(12):1093-100
pubmed: 21057502
Oncol Lett. 2018 Apr;15(4):5220-5226
pubmed: 29552161
Genome Res. 2012 Nov;22(11):2302-14
pubmed: 22745231
Nucleic Acids Res. 2019 Jan 8;47(D1):D1028-D1033
pubmed: 30407549

Auteurs

Zhen Yang (Z)

Center for Medical Research and Innovation of Pudong Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: zhenyang@fudan.edu.cn.

Feng Xu (F)

Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Haizhou Wang (H)

Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Andrew E Teschendorff (AE)

CAS Key Lab of Computational Biology, Shanghai Institute for Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.

Feng Xie (F)

Soochow University, 8 Jixue Road, Suzhou 215131, Jiangsu Province, China.

Yungang He (Y)

Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: heyungang@fudan.edu.cn.

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