Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue.
Colorectal cancer (CRC)
DNA methylation alterations
GRIA4
Gene expression
Gene regulation
Journal
Human cell
ISSN: 1749-0774
Titre abrégé: Hum Cell
Pays: Japan
ID NLM: 8912329
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
24
08
2021
accepted:
23
10
2021
pubmed:
1
11
2021
medline:
5
2
2022
entrez:
31
10
2021
Statut:
ppublish
Résumé
DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology.
Identifiants
pubmed: 34719006
doi: 10.1007/s13577-021-00640-x
pii: 10.1007/s13577-021-00640-x
pmc: PMC8732896
doi:
Substances chimiques
Protein Isoforms
0
Receptors, AMPA
0
glutamate receptor ionotropic, AMPA 4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
310-319Subventions
Organisme : Fondazione Banco di Sardegna
ID : 2012
Organisme : Fondo per la Ricerca Locale (ex 60%), Università di Cagliari
ID : 2012-2021
Organisme : Regione Autonoma della Sardegna
ID : 1C-177
Organisme : Regione Autonoma della Sardegna
ID : CRP-79303
Organisme : Italian University Minister PON-AIM
ID : F74I18000200001
Organisme : Fondazione di Sardegna
ID : Prot. U278.2021/AI.259.RP
Informations de copyright
© 2021. The Author(s).
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