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Updated: Mar 21, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

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Tumor-specific lncRNA IGF1R-AS1 trans-regulates chromatin interactions associated with oncogenic MYC signaling

Yongyong Yang1, Ting-You Wang1, Joshua Fry1,2

  • 1Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Nature Communications
|March 20, 2026
PubMed

Insights

Long non-coding RNAs (lncRNAs) like IGF1R-AS1 regulate cancer. This study shows IGF1R-AS1 drives MYC overexpression via chromatin looping, promoting tumor growth in prostate and lung cancers.

Area of Science:

  • * Molecular biology
  • * Cancer research
  • * Genomics

Background:

  • * Long non-coding RNAs (lncRNAs) are key regulators in cancer development.
  • * Their precise roles are often unclear due to tissue-specific expression and lack of defined functional motifs.
  • * Super-enhancers are crucial regulatory elements in cancer, but their interplay with lncRNAs is not fully understood.

Purpose of the Study:

  • * To investigate the relationship between super-enhancers and lncRNAs in metastatic castration-resistant prostate cancer.
  • * To identify specific lncRNAs associated with super-enhancers and explore their functions.
  • * To elucidate the mechanism by which lncRNAs influence cancer progression via chromatin interactions.

Main Methods:

  • * Comprehensive analysis of lncRNA expression in metastatic castration-resistant prostate cancer patient cohort.
  • * Identification of lncRNAs with super-enhancer associations.
  • * Pan-cancer transcriptome analysis to determine tumor-specific expression.
  • * Investigation of lncRNA interactions with chromatin remodeling complexes and architectural proteins.
  • * Functional assays to assess the impact on MYC expression and tumorigenicity.

Main Results:

  • * Identified 1344 lncRNAs, with IGF1R-AS1 showing the strongest super-enhancer association.
  • * IGF1R-AS1 is specifically transcribed in tumors and overexpressed in prostate and lung cancers.
  • * Revealed a non-canonical trans-acting role for IGF1R-AS1.
  • * IGF1R-AS1 facilitates long-range chromatin looping between distal MYC enhancers and the MYC promoter.
  • * This interaction leads to MYC overexpression and enhanced tumorigenicity.

Conclusions:

  • * IGF1R-AS1 is a tumor-specific, trans-acting lncRNA that modulates oncogenic MYC expression.
  • * It functions by mediating long-range chromatin interactions involving super-enhancers.
  • * IGF1R-AS1 may be a critical player in the pathogenesis of MYC-driven cancers.
  • * This finding suggests IGF1R-AS1 as a potential therapeutic target for specific malignancies.

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