miRNA-193a-5p repression of p73 controls Cisplatin chemoresistance in primary bone tumors

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Osteosarcoma and Ewing Sarcoma are the two most common types of Bone Sarcomas, principally localized at the long bones of the extremities and mainly affecting adolescents and young adults. Cisplatin is one of the current options in the therapeutic arsenal of drugs available to cure these aggressive cancers. Unfortunately, chemoresistance against this agent is still a major cause of patient relapse. Thus, a better understanding of the molecular pathways by which these drugs induce cancer cell death, together with a better delineation of the origins of chemoresistance are required to improve the success rate of current treatments. Furthermore, as p53 is frequently mutated in Bone Sarcomas, other pathways in these cancers must mediate drug-induced cell death. Here, we demonstrate for the first time that TAp73β, a p53-family protein, is implicated in Cisplatin-induced apoptosis of Bone Sarcomas'. Furthermore, while acquired resistance developed by cancer cells against such drugs can have multiple origins, it is now well accepted that epigenetic mechanisms involving microRNAs (miRNAs) are one of them. We show that miRNA-193a-5p modulates the viability, the clonogenic capacity and the Cisplatin-induced apoptosis of the Bone Sarcoma cells through inhibition of TAp73β. Collectively, these results shed light on the involvement of miR-193a-5p in Cisplatin chemoresistance of Bone Sarcomas

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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