간암의 방사선 치료에 의한 exosome의 분비 조절 및 exosomal miRNA 기능연구

Abstract

Tumor-derived exosomal microRNAs are key elements of the cell-cell communications response to lots of stimuli. However, various functions of the exosome in tumor suppression by radiotherapy (RT) are not clearly understood. Our study showed a previously unknown interaction of p53 and histone deacetylase 5 (HDAC5) by radiation exposure in hepatocellular carcinoma (HCC). HDAC5 and p53 interacted by exposure to radiation, which increased exosome release and altered microRNAs' composition within exosomes. Also, we have described the intercommunication occurring between irradiated and untreated cells via exosomal microRNAs that affect tumor proliferation. In particular, the expression of exosomal microRNA 151a-3p (miR-151a-3p) was markedly reduced by radiation treatment. We confirmed that inhibition of exosomal miR-151a-3p promotes suppression of non-irradiated cancer cells, thereby increasing RT sensitivity. In conclusion, our present findings demonstrated HDAC5 is a key component of the p53-mediated release of exosomes resulting in tumor suppression through exosomal miR-151a-3p in response to radiation. Finally, we highlight the important role of exosomal miR-151a-3p as a biomarker in enhancing RT sensitivity.