Related Experiment Video

Updated: Sep 20, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
07:23

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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CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs

Eugenio Morelli1,2, Anil Aktas Samur3,4, Domenico Maisano3,4

  • 1Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.

Blood
|May 22, 2025
PubMed

Insights

Researchers identified hundreds of crucial long noncoding RNA (lncRNA) isoforms essential for cancer cell survival. This discovery highlights their significant oncogenic roles and potential as therapeutic targets in various cancers.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Long noncoding RNAs (lncRNAs) are critical but understudied components of the cancer transcriptome.
  • The specific functions of lncRNA isoforms in cancer remain largely unknown.
  • Understanding lncRNA isoform roles is vital for advancing cancer diagnostics and therapeutics.

Purpose of the Study:

  • To uncover and characterize tumor-essential lncRNA (te-lncRNA) isoforms with clinical relevance using RNA-targeting CRISPR-Cas13d.
  • To investigate the functional roles and subcellular localization of te-lncRNAs in multiple myeloma (MM) and other cancers.
  • To establish a comprehensive resource for studying te-lncRNAs and their therapeutic potential.

Main Methods:

  • Utilized RNA-targeting CRISPR-Cas13d to systematically screen the lncRNA transcriptome in multiple myeloma (MM) tumor cells.
  • Performed functional validation of identified te-lncRNAs in diverse cancer cell lines and animal models.
  • Mapped subcellular localization of te-lncRNAs and assessed the impact of targeting cytosolic isoforms.

Main Results:

  • Identified hundreds of tumor-essential lncRNA (te-lncRNA) isoforms, revealing both MM-specific and pan-cancer dependencies.
  • Discovered over 30 essential cytosolic te-lncRNA isoforms crucial for cancer cell survival.
  • Characterized a specific small nucleolar RNA host gene 6 (SNHG6) isoform involved in proteostasis via interaction with heat shock proteins in the endoplasmic reticulum.
  • Integrated functional and clinical data into the LongDEP Portal, a publicly accessible resource.

Conclusions:

  • te-lncRNAs play significant oncogenic roles and represent promising therapeutic targets.
  • The study provides a comprehensive characterization of te-lncRNAs and their functional importance in cancer.
  • The LongDEP Portal serves as a valuable resource for future research into lncRNAs in oncology.

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