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Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

Xiaonan Liu1,2, Pei Wang1,3, Xufei Teng1,3

  • 1National Genomics Data Center, Beijing Institute of Genomics (China National Center for Bioinformation), Chinese Academy of Sciences, Beijing, China.

Frontiers in Oncology
|March 15, 2021
PubMed
Abstract

Insights

This study reveals how microRNAs and DNA methylation regulate N6-methyladenosine (m6A) regulators across cancers. Aberrant m6A regulator expression impacts cancer progression and survival, offering potential prognostic markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • N6-methyladenosine (m6A) is a crucial mRNA modification regulated by "writers," "erasers," and "readers."
  • Aberrant expression of m6A regulators is linked to cancer development and progression.
  • The precise regulatory mechanisms of m6A regulators in human cancers remain largely unexplored.

Purpose of the Study:

  • To investigate the expression profiles of RNA m6A regulators in human cancers.
  • To identify upstream regulatory mechanisms, including microRNA (miRNA) and DNA methylation, controlling m6A regulator expression.
  • To assess the prognostic significance of these regulatory interactions in cancer patients.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) data for 13 cancer types.
  • Characterization of expression patterns for key m6A regulators (e.g., METTL14, FTO, ALKBH5, YTHDF1, IGF2BP3).
  • Identification of regulatory miRNA and DNA methylation probes (DMPs) associated with m6A regulator expression and patient survival.

Main Results:

  • Down-regulation of METTL14, FTO, and ALKBH5 observed in most cancers; YTHDF1 and IGF2BP3 up-regulated in 12 cancer types.
  • Low expression of certain m6A regulators correlated with improved overall survival.
  • 158 miRNAs and 58 DMPs identified as regulators of m6A expression, with specific pairs showing prognostic value in various cancers, including kidney renal clear cell carcinoma (KIRC).
  • Validation of hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3 pairs in KIRC patients.

Conclusions:

  • Upstream regulation by miRNA and DNA methylation is critical for m6A regulator expression in pan-cancer.
  • Identified regulatory pairs offer potential for prognostic stratification in cancer patients.
  • These findings provide novel insights into the molecular mechanisms of m6A modification in human cancers.
Keywords:
DNA methylationN6-methyladenosineThe Cancer Genome AtlasmicroRNAprognosis

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