Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.
Cell lines
Epithelial to mesenchymal transition
Micro-RNA
Pleural mesothelioma
Thymidylate synthase
Tissue expression
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
21
08
2021
accepted:
05
04
2022
revised:
03
04
2022
pubmed:
25
4
2022
medline:
4
8
2022
entrez:
24
4
2022
Statut:
ppublish
Résumé
The standard front-line treatment for pleural mesothelioma (PM) is pemetrexed-based chemotherapy, whose major target is thymidylate synthase (TS). In several cancer models, miR-215 and miR-375 have been shown to target TS, while information on these miRNAs in PM are still limited although suggest their role in epithelial to mesenchymal transition. Seventy-one consecutive PM tissues (4 biphasic, 7 sarcomatoid, and 60 epithelioid types) and 16 commercial and patient-derived PM cell lines were screened for TS, miR-215, and miR-375 expression. REN and 570B cells were selected for miR-215 and miR-375 transient transfections to test TS modulation. ZEB1 protein expression in tumor samples was also tested. Moreover, genetic profile was investigated by means of BAP1 and p53 immunohistochemistry. Expression of both miR-215 and miR-375 was significantly higher in epithelioid histotype. Furthermore, inverse correlation between TS protein and both miR-215 and miR-375 expression was found. Efficiently transfected REN and 570B cell lines overexpressing miR-215 and miR-375 showed decreased TS protein levels. Epithelioid PM with a mesenchymal component highlighted by reticulin stain showed significantly higher TS and ZEB1 protein and lower miRNA expression. A better survival was recorded for BAP1 lost/TS low cases. Our data indicate that miR-215 and miR-375 are involved in TS regulation as well as in epithelial-to-mesenchymal transition in PM.
Identifiants
pubmed: 35461395
doi: 10.1007/s00428-022-03321-8
pii: 10.1007/s00428-022-03321-8
pmc: PMC9343276
doi:
Substances chimiques
MIRN215 microRNA, human
0
MIRN375 microRNA, human
0
MicroRNAs
0
Thymidylate Synthase
EC 2.1.1.45
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
233-244Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 2019 - ID 23760
Organisme : Regione Piemonte
ID : GR-2011-02348356
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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