Post-transcriptional control drives Aurora kinase A expression in human cancers

Roberta Cacioppo1, Deniz Rad1, Giulia Pagani2

  • 1Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.

Plos One
|November 11, 2024
PubMed

Insights

Aurora kinase A (AURKA) expression is often dysregulated in cancer due to post-transcriptional control. This study reveals that microRNA let-7a and alternative polyadenylation influence AURKA levels, leading to discordant mRNA and protein expression in various cancers.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Aurora kinase A (AURKA) is a key cell cycle regulator implicated in oncogenesis.
  • Elevated AURKA expression is a hallmark of many cancers.
  • Understanding post-transcriptional regulation of AURKA is crucial for cancer biology.

Purpose of the Study:

  • To investigate the role of post-transcriptional mechanisms in controlling AURKA expression across diverse cancer types.
  • To analyze the interplay between AURKA mRNA, protein, hsa-let-7a, and alternative polyadenylation (APA) in cancer.

Main Methods:

  • Meta-analysis of The Cancer Genome Atlas (TCGA) -omics data from 18 cancer types.
  • Correlation and clustering analyses of AURKA mRNA, protein, and hsa-let-7a expression.
  • Measurement of alternative cleavage and polyadenylation (APA) isoform ratios (SLR) for AURKA mRNA.

Main Results:

  • AURKA mRNA levels are generally increased in cancer versus normal tissues.
  • AURKA expression is significantly influenced by post-transcriptional regulation in several cancers.
  • hsa-let-7a and APA isoform switching are implicated in modulating AURKA levels, with varying contributions across cancer types.

Conclusions:

  • AURKA mRNA and protein levels are frequently discordant in cancer due to complex post-transcriptional regulation.
  • The interplay between hsa-let-7a and APA contributes to AURKA dysregulation in specific cancers.
  • Targeting these post-transcriptional mechanisms may offer novel therapeutic strategies for cancer.

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