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

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.