Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion

BACKGROUND Highly upregulated in liver cancer(HULC) is a long non-coding RNA(lnc RNA)which has recently been identified as a key regulator in hepatocellular carcinoma(HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown.AIM To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells.METHODS Serum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery.HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using q PCR and dualluciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTS HULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis(TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, q PCR assays showed that HULC repressed micro RNA-372-3 p(mi R-372-3 p) expression. We also identified Rab11 a as a downstream target of mi R-372-3 p. Dual-luciferase reporter assays suggested that mi R-372-3 p could directly bind both HULC and Rab11 a.CONCLUSION Our findings illustrate the importance of the HULC/mi R-372-3 p/Rab11 a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.