miR-1293 suppresses osteosarcoma progression by modulating drug sensitivity in response to cisplatin treatment.
Int Immunopharmacol
; 130: 111702, 2024 Mar 30.
Article
de En
| MEDLINE
| ID: mdl-38367464
ABSTRACT
Chemotherapy is considered the primary treatment for osteosarcoma. however, its effectiveness is limited due to drug resistance and toxicity. Thus, identifying novel therapeutic targets to enhance the efficacy of chemotherapy is urgently needed. Here, we identified a novel cisplatin-sensitivity enhancing mechanism via up-regulation of the tumour suppressor gene, miR-1293. Meanwhile, higher levels of miR-1293 observed in prechemotherapy patients were associated with a more favorable prognosis. The mechanism underlying cisplatin upregulated miR-1293 expression involves hypomethylation of the miR-1293 promoter, which blocks the binding of the transcription repressor TFAP2A to the promoter. Furthermore, miR-1293 inhibits osteosarcoma progression by targeting TIMP1 to inactivate the Notch1/Hes1 and TGFBR1/Smad2/3 pathways, thereby promoting tumour cell death. The findings presented herein unveil a novel mechanism for enhancing cisplatin sensitivity and proposed a potential therapeutic strategy for osteosarcoma through pre-chemotherapy supplementation of miR-1293.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs osseuses
/
Ostéosarcome
/
MicroARN
Limites:
Humans
Langue:
En
Journal:
Int Immunopharmacol
/
Int. immunopharmacol
/
International immunopharmacology
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Pays-Bas