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Updated: Jun 7, 2025

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
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.
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.
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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