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Pan-cancer characterization of long non-coding RNA and DNA methylation mediated transcriptional dysregulation

Zhen Yang1, Feng Xu2, Haizhou Wang2

  • 1Center for Medical Research and Innovation of Pudong Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Ebiomedicine
|May 27, 2021
PubMed
Abstract

Insights

Cancer epigenetics involves DNA methylation (DNAm) disruptions. This study identifies long noncoding RNA (lncRNA) gene regulatory networks driven by DNAm, revealing new cancer subtype markers and therapeutic targets.

Area of Science:

  • Genomics
  • Epigenetics
  • Cancer Biology

Background:

  • DNA methylation (DNAm) disruption is a hallmark of cancer.
  • Mechanisms altering the cancer methylome require further elucidation.

Purpose of the Study:

  • To systematically identify epigenetically-driven lncRNA-gene regulatory circuits in cancer.
  • To develop an integrative analysis framework for cancer epigenetics research.

Main Methods:

  • Developed MeLncTRN (Methylation mediated LncRNA Transcriptional Regulatory Network) framework.
  • Integrated genome-wide transcriptome, DNA methylome, and copy number variation data.
  • Analyzed 18 cancer types to identify lncRNA-gene regulation.

Main Results:

  • A significant portion of aberrant DNAm and gene expression in cancer is linked to long noncoding RNAs (lncRNAs).
  • Identified distinct lncRNA-gene regulatory patterns specific to or across cancer types.
  • lncRNA modulators are implicated in cancer hallmarks and serve as prognostic markers for cancer subtypes.

Conclusions:

  • Revealed a critical layer of DNAm-associated gene regulation involving lncRNAs in cancer.
  • Provided a valuable database for exploring epigenetically mediated lncRNA-gene interactions in cancer.
Keywords:
DNA methylationLncRNAOmics-data integrationRegulatory networkTranscriptional regulation

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