RNA Sequencing of Plasma Exosomes Revealed Novel Functional lncRNAs in Hepatocellular Carcinoma.

Exosomal long non-coding RNA (lncRNA) has been found to be associated with the development of cancers. However, the expression characteristics and the biological roles of exosomal lncRNAs in hepatocellular carcinoma (HCC) remain unknown. Here, by RNA-sequencing, we found 9,440 mRNAs and 8,572 lncRNAs were differentially expressed (DE-) of plasma-exosomes between HCC patients and healthy controls. Exosomal DE-lncRNAs displayed higher expression level and tissue specificity, lower expression variability and splicing efficiency than DE-mRNAs. Six candidate DE-lncRNAs (fold change≥6, P≤0.01) were high in HCC-cells and cell-exosomes. The knockdown of these candidate DE-lncRNAs significantly affected the migration, proliferation, and apoptosis in HCC-cells. In particular, a novel DE-lncRNA, RP11-85G21.1 (lnc85), promoted HCC cellular proliferation and migration by targeted binding and regulating of miR-324-5p. More importantly, the level of serum lnc85 was highly expressed in both AFP-positive and -negative HCC patients, and allowed distinguishing AFP-negative HCC from healthy control (HC) and liver cirrhosis (LC) (AUC: 0.869, sensitivity: 80.0%, specificity: 76.5%) with high accuracy. Our finding offers a new insight into the association between the dysregulation of exosomal-lncRNA and HCC, suggesting that lnc85 may be a potential biomarker of HCC. This article is protected by copyright. All rights reserved.