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.


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


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