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

Abstract

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.

• Authors: Xuejing Huang, Liyuan Sun, Sha Wen, Deli Deng, Fengjie Wan, Xiao He, Li Tian, Lifang Liang, Chunmeng Wei, Kaiping Gao, Qiang Fu, Yasi Li, Jianning Jiang, Rihong Zhai, Min He
• Journal: Cancer science (Cancer Sci) Vol. 111 Issue 9 Pg. 3338-3349 (Sep 2020) ISSN: 1349-7006 [Electronic] England
• PMID: 32506598 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• Cell-Free Nucleic Acids
• MicroRNAs
• RNA, Long Noncoding
• RNA, Messenger

Topics

• Adult
• Alternative Splicing
• Biomarkers, Tumor
• Carcinoma, Hepatocellular (diagnosis, genetics, metabolism)
• Cell-Free Nucleic Acids
• Exosomes (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• High-Throughput Nucleotide Sequencing
• Humans
• Liver Neoplasms (diagnosis, genetics, metabolism)
• Male
• MicroRNAs
• Middle Aged
• Phenotype
• RNA, Long Noncoding (genetics)
• RNA, Messenger
• ROC Curve
• Sequence Analysis, RNA