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Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene.

Authors :
Cenariu D
Zimta AA
Munteanu R
Onaciu A
Moldovan CS
Jurj A
Raduly L
Moldovan A
Florea A
Budisan L
Pop LA
Magdo L
Albu MT
Tonea RB
Muresan MS
Ionescu C
Petrut B
Buiga R
Irimie A
Gulei D
Berindan-Neagoe I
Source :
Pharmaceutics [Pharmaceutics] 2021 May 06; Vol. 13 (5). Date of Electronic Publication: 2021 May 06.
Publication Year :
2021

Abstract

Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the TP53 gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically TP53 in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the TP53 mutation status of colon cancer cell lines. In TP53 mutated models, miR-125b-5p overexpression slows cancer cells' malignant behavior by inhibiting the invasion/migration and colony formation capacity via direct downregulation of mutated TP53 . In TP53 wild type cells, the exogenous modulation of miR-125b-5p did not significantly affect the molecular and phenotypic profile. In conclusion, our data show that miR-125b-5p has an anti-cancer effect only in TP53 mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies.

Details

Language :
English
ISSN :
1999-4923
Volume :
13
Issue :
5
Database :
MEDLINE
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
34066331
Full Text :
https://doi.org/10.3390/pharmaceutics13050664