Hacking the Cancer Genome: Profiling Therapeutically Actionable Long Non-coding RNAs Using CRISPR-Cas9 Screening

Roberta Esposito; Núria Bosch; Andrés Lanzós; Taisia Polidori; Carlos Pulido-Quetglas; Rory Johnson

doi:10.1016/j.ccell.2019.01.019

Hacking the Cancer Genome: Profiling Therapeutically Actionable Long Non-coding RNAs Using CRISPR-Cas9 Screening

Cancer Cell. 2019 Apr 15;35(4):545-557. doi: 10.1016/j.ccell.2019.01.019. Epub 2019 Feb 28.

Authors

Roberta Esposito¹, Núria Bosch², Andrés Lanzós², Taisia Polidori², Carlos Pulido-Quetglas², Rory Johnson³

Affiliations

¹ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.
² Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
³ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: rory.johnson@dbmr.unibe.ch.

PMID: 30827888
DOI: 10.1016/j.ccell.2019.01.019

Abstract

Long non-coding RNAs (lncRNAs) represent a huge reservoir of potential cancer targets. Such "onco-lncRNAs" have resisted traditional RNAi methods, but CRISPR-Cas9 genome editing now promises functional screens at high throughput and low cost. The unique biology of lncRNAs demands screening strategies distinct from protein-coding genes. The first such screens have identified hundreds of onco-lncRNAs promoting cell proliferation and drug resistance. Ongoing developments will further improve screen performance and translational relevance. This Review aims to highlight the potential of CRISPR screening technology for discovering new onco-lncRNAs, and to guide molecular oncologists wishing to apply it to their cancer of interest.

Keywords: CRISPR-Cas9; cancer; drug targets; genome editing; lncRNA; long non-coding RNA; screening.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / therapeutic use
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
CRISPR-Associated Protein 9 / genetics*
CRISPR-Associated Protein 9 / metabolism
CRISPR-Cas Systems*
Cell Proliferation / drug effects
Cell Proliferation / genetics
Clustered Regularly Interspaced Short Palindromic Repeats*
Drug Resistance, Neoplasm / genetics
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing / methods*
Humans
Molecular Targeted Therapy
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / metabolism
Neoplasms / pathology
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism

Substances

Antineoplastic Agents
Biomarkers, Tumor
RNA, Long Noncoding
CRISPR-Associated Protein 9