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

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 i...

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Main Authors: Roberta Cacioppo, Deniz Rad, Giulia Pagani, Paolo Gandellini, Catherine Lindon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0310625
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author Roberta Cacioppo
Deniz Rad
Giulia Pagani
Paolo Gandellini
Catherine Lindon
author_facet Roberta Cacioppo
Deniz Rad
Giulia Pagani
Paolo Gandellini
Catherine Lindon
author_sort Roberta Cacioppo
collection DOAJ
description 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.
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spelling doaj-art-d61ae3732b5a474cb20cec62bed0e6b72025-08-20T02:05:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011911e031062510.1371/journal.pone.0310625Post-transcriptional control drives Aurora kinase A expression in human cancers.Roberta CacioppoDeniz RadGiulia PaganiPaolo GandelliniCatherine LindonAurora 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.https://doi.org/10.1371/journal.pone.0310625
spellingShingle Roberta Cacioppo
Deniz Rad
Giulia Pagani
Paolo Gandellini
Catherine Lindon
Post-transcriptional control drives Aurora kinase A expression in human cancers.
PLoS ONE
title Post-transcriptional control drives Aurora kinase A expression in human cancers.
title_full Post-transcriptional control drives Aurora kinase A expression in human cancers.
title_fullStr Post-transcriptional control drives Aurora kinase A expression in human cancers.
title_full_unstemmed Post-transcriptional control drives Aurora kinase A expression in human cancers.
title_short Post-transcriptional control drives Aurora kinase A expression in human cancers.
title_sort post transcriptional control drives aurora kinase a expression in human cancers
url https://doi.org/10.1371/journal.pone.0310625
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AT paologandellini posttranscriptionalcontroldrivesaurorakinaseaexpressioninhumancancers
AT catherinelindon posttranscriptionalcontroldrivesaurorakinaseaexpressioninhumancancers