Abstract LB-B03: miR-24 acts as a tumor suppressor and radiosensitizer by targeting Jab1/CSN5 functions

Abstract Radiotherapy is the standard therapy for head and neck cancer; however, radioresistance can hinder successful treatment and is likely to give rise to local recurrence and distant metastatic relapse. Recent studies revealed the role of microRNA (miRNA)-mRNA mediated regulation in tumorigenesis; however, whether specific miRNAs regulate tumor radioresistance and can be exploited as radiosensitizing agents remains unclear. The purpose of this study was to identify an miRNA signature from differentially expressed miRNAs in radioresistance. Here, we report that miR-24 acts as a tumor suppressor and radiosensitizer in nasopharyngeal carcinoma (NPC) cells and mouse models by targeting Jab1/CSN5 and that loss of miR-24 is highly associated with poor survival. When combined with irradiation, miR-24 acted as a radiosensitizer in NPC cells. Jab1/CSN5 functioned in a manner opposite that of miR-24 in NPC tumorigenesis and radioresistance. We demonstrated that miR-24 inhibits Jab1/CSN5 translation, leading to tumor growth inhibition, and sensitizes NPC tumors to radiation in vivo. Moreover, miR-24 inhibits DNA damage repair by targeting JAB1/CSN5. Finally, comparative analysis of paired samples of primary and matched recurrent NPC tissues showed that miR-24 levels were significantly lower and Jab1/CSN5 levels were higher in recurrent NPC than in primary NPC. Our findings identify miR-24 as a tumor suppressor and radiosensitizer miRNA and reveal a new therapeutic strategy for radioresistant tumors. Citation Format: Francois X. Claret, Sumei Wang, Yunbao Pan, Huiling Yang. miR-24 acts as a tumor suppressor and radiosensitizer by targeting Jab1/CSN5 functions. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B03.