1. Academic Validation
  2. Identification of exosomal hsa-miR-483-5p as a potential biomarker for hepatocellular carcinoma via microRNA expression profiling of tumor-derived exosomes

Identification of exosomal hsa-miR-483-5p as a potential biomarker for hepatocellular carcinoma via microRNA expression profiling of tumor-derived exosomes

  • Exp Cell Res. 2022 Aug 15;417(2):113232. doi: 10.1016/j.yexcr.2022.113232.
Jie Lin 1 Wansong Lin 2 Yannan Bai 3 Yanling Liao 4 Qiaoyan Lin 5 Lingfeng Chen 1 Yijuan Wu 1
Affiliations

Affiliations

  • 1 Department of Pathology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China.
  • 2 Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China. Electronic address: [email protected].
  • 3 Department of Hepatobiliopancreatic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China.
  • 4 Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China.
  • 5 Department of Blood Transfusion, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, China.
Abstract

To date, most studies of exosomes related to hepatocellular carcinoma (HCC) have used commercial Cancer cell lines or patient plasma as source material. In this study, we isolated exosomes directly from HCC tissues to investigate the potential of exosomal contents as biomarkers for HCC. Exosomes were identified and verified using transmission electron microscopy, nano-flow cytometry analysis, and western blotting. Tissue-derived exosomal miRNA expression was profiled by high-throughput sequencing, and differential expression of miRNAs was validated by quantitative real-time polymerase chain reaction analysis. The diagnostic performance of differentially expressed exosomal miRNAs for HCC was evaluated by receiver operating characteristic curve analysis. Target genes of these miRNAs were verified using luciferase reporter assays, and their functions were studied through in vitro and rescue assays. In total, 225 differentially expressed exosomal miRNAs were identified in HCC samples compared with adjacent liver tissues, and some were associated with HCC tumorigenesis and progression. Comparison of the expression profiles of tissue-derived and plasma-derived exosomal miRNAs identified hsa-miR-483-5p as the only differentially expressed miRNA detected in both HCC tissue and plasma, and this was in a validation group of HCC patients. Analysis of the diagnostic performance of plasma exosomal hsa-miR-483-5p or plasma hsa-miR-483-5p found that both could differentiate HCC and non-HCC cases. In vitro ectopic miR-483-5p expression promoted HCC cell proliferation. CDK15 was confirmed to bind with miR-483-5p directly, and thus, miR-483-5p may function by downregulating CDK15. Hsa-miR-483-5p represents a potential specific and sensitive biomarker for HCC diagnosis.

Keywords

Biomarker; Hepatocellular carcinoma; Plasma-derived exosomes; Sequencing; Tissue-derived exosomes; microRNA.

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