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Updated: Sep 8, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
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Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

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Systematic lncRNA mapping to genome-wide co-essential modules uncovers cancer dependency on uncharacterized lncRNAs

Ramkrishna Mitra1, Clare M Adams1, Christine M Eischen1

  • 1Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, United States.

Elife
|June 13, 2022
PubMed

Insights

Researchers identified essential long noncoding RNAs (lncRNAs) regulating cancer cell proliferation using CRISPR screens and multi-omics data. Two novel lncRNAs, PSLR-1 and PSLR-2, were found to suppress tumor growth by arresting the cell cycle.

Area of Science:

  • Genomics
  • Cancer Biology
  • RNA Biology

Background:

  • Genome-scale CRISPR screens identify essential genes in cancer cell lines.
  • Long noncoding RNAs (lncRNAs) are crucial regulators, but their essentiality is understudied due to limited loss-of-function screening methods.
  • Uncharacterized lncRNAs play significant roles in cellular processes, yet many remain undiscovered.

Purpose of the Study:

  • To develop a method for identifying essential lncRNAs using integrated genomic and transcriptomic data.
  • To discover novel lncRNAs that regulate cancer cell proliferation and growth.
  • To prioritize lncRNAs with potential as pan-cancer therapeutic targets.

Main Methods:

  • Integrated analysis of copy number, epigenetic, and transcriptomic data from over 800 cancer cell lines.
  • Utilized CRISPR-derived co-essential pathway information to predict lncRNA dependencies.
  • Prioritized lncRNAs based on dependency across cancer types and response to growth inhibitors.

Main Results:

  • Successfully recapitulated known essential lncRNAs and predicted 289 poorly characterized lncRNAs involved in proliferation.
  • Identified 30 high-confidence lncRNAs regulating proliferation across multiple cancer types.
  • Characterized two novel proliferation-suppressive lncRNAs (PSLR-1, PSLR-2) regulated by p53 and linked to patient survival.

Conclusions:

  • The study provides a powerful resource for lncRNA discovery in cancer, overcoming current screening limitations.
  • PSLR-1 and PSLR-2 modulate the FOXM1 network to induce G2 cell cycle arrest, inhibiting cancer proliferation.
  • These findings highlight the potential of lncRNAs as therapeutic targets in oncology.
Keywords:
cancer dependencycell cycleco-essential networkscomputational biologyhumanlong non-coding RNAproliferationsystems biology

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