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

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.