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Research Paper|Volume 12, Issue 12|pp 11843—11863

Serum exosomal long noncoding RNAs lnc-FAM72D-3 and lnc-EPC1-4 as diagnostic biomarkers for hepatocellular carcinoma

Zhicheng Yao1, Changchang Jia2, Yan Tai3, Hao Liang1, Zhaozhong Zhong4, Zhiyong Xiong1, Meihai Deng4, Qi Zhang2
  • 1Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
  • 2Department of Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
  • 3Department of Liver Disease Lab, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
  • 4Department of Hepatobilliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
* Co-first author and Equal contribution
Received: October 22, 2019Accepted: May 1, 2020Published: June 18, 2020
https://doi.org/10.18632/aging.103355

Copyright © 2020 Yao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long noncoding RNAs (lncRNAs), such as LINC00462, HOTAIR, and MALAT1, are significantly upregulated in hepatocellular carcinoma (HCC) tissues. However, lncRNA expression in the serum of HCC patients is still unclear. To identify candidate lncRNAs for HCC diagnosis, we purified exosomal total RNA from the serum of healthy volunteers (controls) and hepatitis, cirrhosis, and HCC patients. To assess the function of lncRNAs, small interfering RNAs and overexpression vectors were designed and cell viability and cell apoptosis assays conducted. The exosomes of the control group had a larger number of lncRNAs with a high amount of alternative splicing compared to hepatic disease patients. qPCR assays showed that lnc-FAM72D-3, lnc-GPR89B-15, lncZEB2-19, and lnc-EPC1-4 are differentially expressed in HCC. Furthermore, the expression level of lnc-EPC1-4 correlated with age. While the expression levels of lnc-GPR89B-15 and lnc-EPC1-4 correlated with serum alpha-fetoprotein level. lnc-FAM72D-3 knockdown decreased cell viability and promoted cell apoptosis, indicating that lnc-FAM72D-3 functions as an oncogene in HCC. In contrast, lnc-EPC1-4 overexpression inhibited cell proliferation and induced cell apoptosis, indicating that it functions as a tumor suppressor gene. Collectively, these findings show that lnc-FAM72D-3 and lnc-EPC1-4 play a novel role that might contribute to hepatocarcinogenesis and identify potential candidate biomarkers for HCC diagnosis.