Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Inhibition of homologous recombination repair by Mirin in ovarian cancer ameliorates carboplatin therapy response in vitro

J. Horak, D. Vallusova, A. Cumova, P. Holy, P. Vodicka, A. Opattova

. 2025 ; 40 (1) : 87-95. [pub] 20250315

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25009498

Grantová podpora
19-10543S Czech Science Foundation

Chemoresistance poses one of the most significant challenges of cancer therapy. Carboplatin (CbPt) is one of the most used chemotherapeutics in ovarian cancer (OVC) treatment. MRE11 constitutes a part of homologous recombination (HR), which is responsible for the repair of CbPt-induced DNA damage, particularly DNA crosslinks. The study's main aim was to address the role of HR in CbPt chemoresistance in OVC and to evaluate the possibility of overcoming CbPt chemoresistance by Mirin-mediated MRE11 inhibition in an OVC cell line. Lower expression of MRE11 was associated with better overall survival in a cohort of OVC patients treated with platinum drugs (TCGA dataset, P < 0.05). Using in vitro analyses, we showed that the high expression of HR genes drives the CbPt chemoresistance in our CbPt-resistant cell line model. Moreover, the HR inhibition by Mirin not only increased sensitivity to carboplatin (P < 0.05) but also rescued the sensitivity in the CbPt-resistant model (P < 0.05). Our results suggest that MRE11 inhibition with Mirin may represent a promising way to overcome OVC resistance. More therapy options will ultimately lead to better personalized cancer therapy and improvement of patients' survival.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25009498
003      
CZ-PrNML
005      
20250429134741.0
007      
ta
008      
250415s2025 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/mutage/gead036 $2 doi
035    __
$a (PubMed)38099488
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Horak, Josef $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine Czech Academy of Sciences (CAS), 142 20 Prague, Czech Republic $u Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic
245    10
$a Inhibition of homologous recombination repair by Mirin in ovarian cancer ameliorates carboplatin therapy response in vitro / $c J. Horak, D. Vallusova, A. Cumova, P. Holy, P. Vodicka, A. Opattova
520    9_
$a Chemoresistance poses one of the most significant challenges of cancer therapy. Carboplatin (CbPt) is one of the most used chemotherapeutics in ovarian cancer (OVC) treatment. MRE11 constitutes a part of homologous recombination (HR), which is responsible for the repair of CbPt-induced DNA damage, particularly DNA crosslinks. The study's main aim was to address the role of HR in CbPt chemoresistance in OVC and to evaluate the possibility of overcoming CbPt chemoresistance by Mirin-mediated MRE11 inhibition in an OVC cell line. Lower expression of MRE11 was associated with better overall survival in a cohort of OVC patients treated with platinum drugs (TCGA dataset, P < 0.05). Using in vitro analyses, we showed that the high expression of HR genes drives the CbPt chemoresistance in our CbPt-resistant cell line model. Moreover, the HR inhibition by Mirin not only increased sensitivity to carboplatin (P < 0.05) but also rescued the sensitivity in the CbPt-resistant model (P < 0.05). Our results suggest that MRE11 inhibition with Mirin may represent a promising way to overcome OVC resistance. More therapy options will ultimately lead to better personalized cancer therapy and improvement of patients' survival.
650    12
$a karboplatina $x farmakologie $x terapeutické užití $7 D016190
650    _2
$a lidé $7 D006801
650    12
$a nádory vaječníků $x farmakoterapie $x genetika $7 D010051
650    _2
$a ženské pohlaví $7 D005260
650    12
$a rekombinační oprava DNA $x účinky léků $7 D059767
650    _2
$a nádorové buněčné linie $7 D045744
650    12
$a chemorezistence $x genetika $x účinky léků $7 D019008
650    12
$a homologní protein MRE11 $x genetika $7 D000076228
650    _2
$a protinádorové látky $x farmakologie $x terapeutické užití $7 D000970
650    _2
$a regulace genové exprese u nádorů $x účinky léků $7 D015972
650    _2
$a poškození DNA $x účinky léků $7 D004249
655    _2
$a časopisecké články $7 D016428
700    1_
$a Vallusova, Dominika $u Faculty of Science, Charles University, 128 00 Prague, Czech Republic
700    1_
$a Cumova, Andrea $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine Czech Academy of Sciences (CAS), 142 20 Prague, Czech Republic $u First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic
700    1_
$a Holy, Petr $u Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic $u Toxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech Republic $1 https://orcid.org/0000000269505563
700    1_
$a Vodicka, Pavel $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine Czech Academy of Sciences (CAS), 142 20 Prague, Czech Republic $u First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic
700    1_
$a Opattova, Alena $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine Czech Academy of Sciences (CAS), 142 20 Prague, Czech Republic $u First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic $u Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic
773    0_
$w MED00003429 $t Mutagenesis $x 1464-3804 $g Roč. 40, č. 1 (2025), s. 87-95
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38099488 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250415 $b ABA008
991    __
$a 20250429134736 $b ABA008
999    __
$a ok $b bmc $g 2311094 $s 1246579
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2025 $b 40 $c 1 $d 87-95 $e 20250315 $i 1464-3804 $m Mutagenesis $n Mutagenesis $x MED00003429
GRA    __
$a 19-10543S $p Czech Science Foundation
LZP    __
$a Pubmed-20250415

Najít záznam

Citační ukazatele

Možnosti archivace