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

PLoS One. 2024 Nov 11;19(11):e0310625. doi: 10.1371/journal.pone.0310625. eCollection 2024.

Abstract

Aurora kinase A (AURKA) is a major regulator of the cell cycle. A prominent association exists between high expression of AURKA and cancer, and impairment of AURKA levels can trigger its oncogenic activity. In order to explore the contribution of post-transcriptional regulation to AURKA expression in different cancers, we carried out a meta-analysis of -omics data of 18 cancer types from The Cancer Genome Atlas (TCGA). Our study confirmed a general trend for increased AURKA mRNA in cancer compared to normal tissues and revealed that AURKA expression is highly dependent on post-transcriptional control in several cancers. Correlation and clustering analyses of AURKA mRNA and protein expression, and expression of AURKA-targeting hsa-let-7a miRNA, unveiled that hsa-let-7a is likely involved to varying extents in controlling AURKA expression in cancers. We then measured differences in the short/long ratio (SLR) of the two alternative cleavage and polyadenylation (APA) isoforms of AURKA mRNA across cancers compared to the respective healthy counterparts. We suggest that the interplay between APA and hsa-let-7a targeting of AURKA mRNA may influence AURKA expression in some cancers. hsa-let-7a and APA may also independently contribute to altered AURKA levels. Therefore, we argue that AURKA mRNA and protein expression are often discordant in cancer as a result of dynamic post-transcriptional regulation.

Publication types

  • Meta-Analysis

MeSH terms

  • Aurora Kinase A* / genetics
  • Aurora Kinase A* / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasms* / genetics
  • Polyadenylation
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Aurora Kinase A
  • AURKA protein, human
  • MicroRNAs
  • RNA, Messenger
  • mirnlet7 microRNA, human

Grants and funding

We were funded by the Department of Pharmacology to Roberta Cacioppo and UKRI | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R004137/1) to Catherine Lindon. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.