Exosomal miRNA-720 as a potential diagnostic and prognostic biomarker for hepatocellular carcinoma.

[BACKGROUND/AIMS] Circulating exosomal microRNAs (miRNAs) can serve as diagnostic and prognostic biomarkers for cancer. This study aimed to identify specific miRNAs in serum exosomes of patients with hepatocellular carcinoma (HCC) and validate their biological functions as novel diagnostic and predictive biomarkers.

[METHODS] Serum exosomal miRNAs in patients with HCC (n = 241) and without HCC (n = 45) were measured by qRT-PCR. The role of exosomal miRNAs in HCC was investigated through in vitro tests and verified in a clinical cohort of patients.

[RESULTS] In vitro, we observed delivery of exosomal miRNA-720 (miR-720) to recipient cells. Exosome-mediated miR-720 promoted proliferation and inhibited apoptosis of recipient HCC cells. Exosomal miR-720 inhibited tumor suppressor StarD13 expression in recipient cells. Additionally, exosomal miR-720 promoted stemness in recipient cells by increasing protein expression of stemness-associated markers such as OCT4 and c-MYC. In our cohort, serum exosomal miR-720 was significantly upregulated in HCC patients than in non-HCC patients, showing an excellent diagnostic performance for HCC. Particularly, exosomal miR-720 exhibited superior performance in diagnosing small HCC (< 2 cm) compared to AFP or DCP. Exosomal miR-720 levels positively correlated with advancing tumor stage and size. Patients with high expression of exosomal miR-720 had significantly shorter time to progression than those with low expression of exosomal miR-720 during transarterial chemoembolization (TACE).

[CONCLUSION] Our results demonstrate that exosomal miR-720 plays an oncogenic role in HCC by targeting StarD13. Circulating exosomal miR-720 could be used as a novel diagnostic and therapeutic biomarker and serve as a guide for selecting treatment options including TACE for HCC.