Evidence mapPaperPMID 40403231Full record

ArticleBlood2025

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

Eugenio Morelli, Anil Aktas-Samur, Domenico Maisano, Claire Gao, Vanessa Favasuli, Dimitrios Papaioannou, Giovanni De Nola, Jon E Henninger, Na Liu, Marcello Turi and 12 more

Abstract read
In one paragraph

Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. TheNon-coding RNA · 2025
    Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Eugenio MorelliCandiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.ORCID 0000-0002-8850-0442
Anil Aktas-SamurDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.ORCID 0000-0002-0183-0562
Domenico MaisanoDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Claire GaoDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Vanessa FavasuliDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Dimitrios PapaioannouPerlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
Giovanni De NolaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.ORCID 0009-0008-9889-1134
Jon E HenningerWhitehead Institute of Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA.ORCID 0000-0002-9604-2007
Na LiuDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Marcello TuriCandiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.ORCID 0000-0002-8760-1794
Pietro FolinoDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Laure VreuxDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.ORCID 0009-0005-1387-6129
Michela CumerlatoDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.ORCID 0009-0006-8229-3047
Liang ChenDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Iannis AifantisDepartment of Pathology, New York University Grossman School of Medicine, New York, NY.
Mariateresa FulcinitiDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Kenneth C AndersonDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Abigail K R Lytton-JeanDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.ORCID 0000-0002-1582-0066
Annamaria GullàCandiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia-Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy.
Richard A YoungWhitehead Institute of Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA.ORCID 0000-0001-8855-8647
Mehmet K SamurDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.
Nikhil C MunshiDepartment of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA.

Funding

Project 4: Targeting genomic instability and evolution in myelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · 2023 to 2025
$7.4M
Mechanisms of enhancer regulation in leukemiaR01CA228135 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Iannis Aifantis · 2022 to 2023
$985k
Mapping and targeting 3D regulatory elements in leukemia and lymphoma-SupplementR01CA298153 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2025 to 2025
$935k
NCI NIH HHS P01 CA155258NCI NIH HHS R01 CA228135NCI NIH HHS R01 CA298153
6 · The paper itself

Abstract

abstractLong noncoding RNAs (lncRNAs) are a significant yet largely uncharted component of the cancer transcriptome, with their isoform-specific functions remaining poorly understood. In this study, we used RNA-targeting CRISPR-Cas13d to uncover and characterize hundreds of tumor-essential lncRNA (te-lncRNA) isoforms with clinical relevance. Focusing on multiple myeloma (MM), we targeted the lncRNA transcriptome expressed in tumor cells from patients with MM and revealed both MM-specific and pan-cancer dependencies across diverse cancer cell lines, which we further validated in animal models. Additionally, we mapped the subcellular localization of these te-lncRNAs, identifying >30 cytosolic isoforms that proved essential when targeted by cytosol-localized Cas13d. Notably, a specific isoform of small nucleolar RNA host gene 6, enriched in the endoplasmic reticulum, interacts with heat shock proteins to maintain cellular proteostasis. We also integrated functional and clinical data into the publicly accessible LongDEP Portal, providing a valuable resource for the research community. Our study offers a comprehensive characterization of te-lncRNAs, underscoring their oncogenic roles and therapeutic potential.

Indexed as

CRISPR-Cas SystemsMultiple MyelomaNeoplasmsRNA, Long NoncodingTranscriptomeAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceRNA IsoformsRNA IsoformsRNA, Long Noncoding

Identifiers

PMID40403231
PMCPMC12783513

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.