Top Med Chem (2020) 33: 401–428
DOI: 10.1007/7355_2019_83
© Springer Nature Switzerland AG 2019
Published online: 24 October 2019
Altered Long Non-coding RNA Expression
in Cancer: Potential Biomarkers
and Therapeutic Targets?
David Hanly, Manel Esteller, and María Berdasco
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
2 lncRNAs in Epigenetic Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
2.1 Histone Modification and Transcriptional Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
2.2 LncRNA Epitranscriptomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
2.3 Nuclear Architecture and 3D Genome Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
2.4 Alternative Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
2.5 Crosstalk with miRNAs: Competing Endogenous ncRNAs . . . . . . . . . . . . . . . . . . . . . . . . . 408
3 lncRNA and Epigenetic Deregulation in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
3.1 Oncogenic lncRNAs: HOTAIR, MALAT1, TUG1 and MIAT . . . . . . . . . . . . . . . . . . . . . . 409
3.2 Tumour-Suppressive lncRNAs: lincRNA-p21 and TP53BP1 . . . . . . . . . . . . . . . . . . . . . . . 412
4 Strategies to Target lncRNAs Implicated in Cancer Therapy Resistance . . . . . . . . . . . . . . . . . . 413
4.1 HOTAIR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
4.2 MALAT1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
4.3 TUG1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
5 Conclusion and Future Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
Abstract Long non-coding RNAs (lncRNAs) have been implicated in a wide range
of biological processes. One of the most striking functions of lncRNAs is their
capacity to act as “backstage” sculptors of the epigenetic landscape by interacting
with chromatin-modifying proteins and directing their activities. LncRNAs can
D. Hanly and M. Berdasco (*)
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Barcelona,
Spain
e-mail: mberdasco@carrerasresearch.org
M. Esteller
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Barcelona,
Spain
Department of Physiological Sciences II, School of Medicine, University of Barcelona,
Barcelona, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
DOI: 10.1007/7355_2019_83
© Springer Nature Switzerland AG 2019
Published online: 24 October 2019
Altered Long Non-coding RNA Expression
in Cancer: Potential Biomarkers
and Therapeutic Targets?
David Hanly, Manel Esteller, and María Berdasco
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
2 lncRNAs in Epigenetic Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
2.1 Histone Modification and Transcriptional Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
2.2 LncRNA Epitranscriptomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
2.3 Nuclear Architecture and 3D Genome Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
2.4 Alternative Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
2.5 Crosstalk with miRNAs: Competing Endogenous ncRNAs . . . . . . . . . . . . . . . . . . . . . . . . . 408
3 lncRNA and Epigenetic Deregulation in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
3.1 Oncogenic lncRNAs: HOTAIR, MALAT1, TUG1 and MIAT . . . . . . . . . . . . . . . . . . . . . . 409
3.2 Tumour-Suppressive lncRNAs: lincRNA-p21 and TP53BP1 . . . . . . . . . . . . . . . . . . . . . . . 412
4 Strategies to Target lncRNAs Implicated in Cancer Therapy Resistance . . . . . . . . . . . . . . . . . . 413
4.1 HOTAIR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
4.2 MALAT1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
4.3 TUG1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
5 Conclusion and Future Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
Abstract Long non-coding RNAs (lncRNAs) have been implicated in a wide range
of biological processes. One of the most striking functions of lncRNAs is their
capacity to act as “backstage” sculptors of the epigenetic landscape by interacting
with chromatin-modifying proteins and directing their activities. LncRNAs can
D. Hanly and M. Berdasco (*)
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Barcelona,
Spain
e-mail: mberdasco@carrerasresearch.org
M. Esteller
Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Barcelona,
Spain
Department of Physiological Sciences II, School of Medicine, University of Barcelona,
Barcelona, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain