Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence.
A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the impact of circulating exosomes on HCC development and recurrence. One-shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha-fetoprotein (AFP), but exosome-free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR-92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR-92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR-92b. The hepatoma-derived exosomal miR-92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell-mediated cytotoxicity. Furthermore, higher expression of miR-92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma-derived exosomal miR-92b. The value of circulating exosomal miR-92b may predict the risk of posttransplant HCC recurrence.
['Nakano|Toshiaki|T|0000-0003-3701-3449', 'Chen|I-Hsuan|IH|', 'Wang|Chih-Chi|CC|', 'Chen|Po-Jung|PJ|', 'Tseng|Hui-Peng|HP|', 'Huang|Kuang-Tzu|KT|', 'Hu|Tsung-Hui|TH|', 'Li|Lung-Chih|LC|', 'Goto|Shigeru|S|', 'Cheng|Yu-Fan|YF|', 'Lin|Chih-Che|CC|', 'Chen|Chao-Long|CL|']
D000818:Animals D014408:Biomarkers, Tumor D006528:Carcinoma, Hepatocellular D049109:Cell Proliferation D055354:Exosomes D005260:Female D015972:Gene Expression Regulation, Neoplastic D008114:Liver Neoplasms, Experimental D016031:Liver Transplantation D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D035683:MicroRNAs D009364:Neoplasm Recurrence, Local D011183:Postoperative Complications D051381:Rats
basic (laboratory) research/science biomarker cancer/malignancy/neoplasia: risk factors cellular biology immunobiology liver transplantation/hepatology microarray/gene array molecular biology: micro RNA natural killer (NK) cells/NK receptors translational research/science