miR-1293 suppresses osteosarcoma progression by modulating drug sensitivity in response to cisplatin treatment

Copyright © 2024. Published by Elsevier B.V..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:130

Enthalten in:

International immunopharmacology - 130(2024) vom: 30. März, Seite 111702

Sprache:

Englisch

Beteiligte Personen:

Wang, Tingxuan [VerfasserIn]
Huang, Jincheng [VerfasserIn]
Chen, Gang [VerfasserIn]
Fu, Jiahui [VerfasserIn]
Li, Tian [VerfasserIn]
Zou, Xuenong [VerfasserIn]
Yi, Hualin [VerfasserIn]

Links:

Volltext

Themen:

Chemotherapy
Cisplatin
Journal Article
MIRN1293 microRNA, human
Methylation
MiRNA
MicroRNAs
Osteosarcoma
Q20Q21Q62J
TFAP2A
TIMP1

Anmerkungen:

Date Completed 25.03.2024

Date Revised 25.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2024.111702

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36857525X