Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5283
Peer-review started: April 26, 2019
First decision: May 24, 2019
Revised: June 7, 2019
Accepted: July 19, 2019
Article in press: May 24, 2019
Published online: September 21, 2019
Processing time: 148 Days and 22.5 Hours
Highly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) 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.
To explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells.
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 qPCR and dual-luciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.
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, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a.
Our findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.
Core tip: We found that (1) HULC expression was higher in serum exosomes of patients with HCC than in those of healthy controls, and higher in liver cancer tissues than in tumor adjacent tissues; (2) HULC expression in serum exosomes and liver cancer tissues were correlated with the TNM classification, and HULC expression in tissues was correlated with that in serum exosomes; (3) Increased HULC expression was associated with increased proliferation and invasion and reduced apoptosis of HCC cells; and (4) HULC repressed miR-372-3p expression, and miR-372-3p could directly bind both HULC and Rab11a. Furthermore, the HULC/ miR-372-3p /Rab11a axis promoted the secretion of exosomes from HCC cells.