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

Roberta Esposito1, Núria Bosch2, Andrés Lanzós2

  • 1Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.

Cancer Cell
|March 5, 2019
PubMed

Insights

CRISPR-Cas9 genome editing enables high-throughput screening for cancer targets like long non-coding RNAs (lncRNAs). These novel onco-lncRNAs promote cancer cell proliferation and drug resistance, offering new therapeutic avenues.

Area of Science:

  • Molecular Oncology
  • Genomics
  • RNA Biology

Background:

  • Long non-coding RNAs (lncRNAs) are increasingly recognized as critical players in cancer development.
  • Traditional RNA interference (RNAi) methods have limitations in targeting lncRNAs effectively.
  • CRISPR-Cas9 genome editing offers a powerful, cost-effective approach for functional genomic screening.

Purpose of the Study:

  • To review the potential of CRISPR-Cas9 screening for discovering novel oncogenic long non-coding RNAs (onco-lncRNAs).
  • To guide molecular oncologists in applying CRISPR screening strategies for their specific cancer research.
  • To highlight the distinct screening requirements for lncRNAs compared to protein-coding genes.

Main Methods:

  • Utilizing CRISPR-Cas9 genome editing for high-throughput functional screens.
  • Developing screening strategies tailored to the unique biology of lncRNAs.
  • Analyzing results from initial screens to identify onco-lncRNAs.

Main Results:

  • The first CRISPR-based screens have identified hundreds of onco-lncRNAs.
  • These identified onco-lncRNAs are implicated in promoting cancer cell proliferation.
  • Several onco-lncRNAs were found to confer drug resistance in cancer cells.

Conclusions:

  • CRISPR screening technology holds significant promise for the discovery of new onco-lncRNAs.
  • Advancements in screening methodologies will enhance performance and translational relevance.
  • This approach provides a valuable tool for molecular oncologists to investigate lncRNA functions in cancer.
Keywords:
CRISPR-Cas9cancerdrug targetsgenome editinglncRNAlong non-coding RNAscreening

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