Journal Article

RNA sequencing of plasma exosomes revealed novel functional long noncoding RNAs in hepatocellular carcinoma

Zhai, Rihong, Liang, Lifang, Li, Yasi, Huang, Xuejing, Wei, Chunmeng, Tian, Li, Sun, Liyuan, Fu, Qiang, Deng, Deli, Jiang, Jianning, Wen, Sha, He, Min, He, Xiao, Wan, Fengjie, Gao, Kaiping

2020

Overview

Exosomal long noncoding 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 9440 mRNAs and 8572 lncRNAs were differentially expressed (DE‐) in plasma exosomes between HCC patients and healthy controls. Exosomal DE‐lncRNAs displayed higher expression levels and tissue specificity, lower expression variability and splicing efficiency than DE‐mRNAs. Six candidate DE‐lncRNAs (fold change 6 or more, P ≤ .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 Alpha‐fetoprotein (AFP)‐positive and AFP‐negative HCC patients and allowed distinguishing AFP‐negative HCC from healthy control and liver cirrhosis (area under the receiver operating characteristic curve, 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 could be a potential biomarker of HCC. Long noncoding RNAs (lncRNAs) and mRNAs are aberrantly expressed in plasma exosomes of hepatocellular carcinoma (HCC). Exosomal lncRNAs could have greater potential to serve as the biomarkers of HCC than mRNAs. Exosomal lncRNAs participate in the regulation of cell biology processes. RP11‐85G21.1 promotes proliferation of HCC cell lines by acting as a sponge of microRNA‐324‐5p.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / Age / Alternative Splicing / Apoptosis / Biomarkers / Biomarkers, Tumor / Carcinoma, Hepatocellular - diagnosis / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - metabolism / Cell adhesion & migration / Cell proliferation / Cell-Free Nucleic Acids / Cirrhosis / Exosomes / Exosomes - metabolism / Female / Gene Expression Regulation, Neoplastic / Hepatocellular carcinoma / High-Throughput Nucleotide Sequencing / Humans / Liver cancer / Liver cirrhosis / Liver Neoplasms - diagnosis / Liver Neoplasms - genetics / Liver Neoplasms - metabolism / long noncoding RNA / Male / Medical prognosis / MicroRNAs / Middle Aged / miR‐324‐5p / Original / Phenotype / Plasma / plasma exosome / Proteins / Ribonucleic acid / RNA / RNA, Long Noncoding - genetics / RNA, Messenger / ROC Curve / RP11‐85G21.1 / Sequence Analysis, RNA / Splicing / Tumorigenesis