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Updated: May 14, 2026

An Enrichment Method for Small Extracellular Vesicles Derived from Liver Cancer Tissue
10:33

An Enrichment Method for Small Extracellular Vesicles Derived from Liver Cancer Tissue

Published on: February 3, 2023

Exosomal circRNA_0023016 suppresses hepatocellular carcinoma progression by regulating the EIF4A3/RNF113A/CXCR4 axis

Tianqi Wang1, Weiwei Li1, Anhai Yu1

  • 1Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

International Immunopharmacology
|May 12, 2026
PubMed

Insights

A novel exosomal circRNA_0023016 pathway regulates angiogenesis in hepatocellular carcinoma (HCC). This pathway involves eukaryotic translation initiation factor 4A3 (EIF4A3), ring finger protein 113A (RNF113A), and C-X-C chemokine receptor type 4 (CXCR4), offering a potential therapeutic target for high-invasion HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) invasion and metastasis are linked to angiogenesis.
  • Mechanisms regulating angiogenesis in HCC remain largely unknown.
  • Exosomal circRNAs are emerging as key regulators in cancer progression.

Purpose of the Study:

  • To identify novel molecular players involved in HCC angiogenesis.
  • To investigate the role of circRNA_0023016 in HCC invasion and metastasis.
  • To elucidate the regulatory axis of exosomal circRNA_0023016 in angiogenesis.

Main Methods:

  • Bioinformatic analysis of the GSE121714 database to identify candidate circRNAs.
  • Expression analysis of circRNA_0023016 in HCC cell lines, tissues, and serum exosomes.
  • Functional assays in human umbilical vein endothelial cells (HUVECs) to assess the impact of circRNA_0023016 inhibition.
  • RNA-protein binding assays and interaction studies.
  • Ubiquitination and proteasomal degradation assays.
  • Flow sorting of angiogenic endothelial cells from mouse HCC tissues.

Main Results:

  • circRNA_0023016 was found to be downregulated in high invasion HCC.
  • Inhibition of exosomal circRNA_0023016 affected the expression of EIF4A3, RNF113A, and CXCR4.
  • EIF4A3 binds to circRNA_0023016 and interacts with RNF113A.
  • RNF113A regulates CXCR4 stability by preventing its ubiquitination and degradation.
  • A novel exosomal circRNA_0023016/EIF4A3/RNF113A/CXCR4 axis was identified in HCC.

Conclusions:

  • Exosomal circRNA_0023016 plays a critical role in regulating angiogenesis in HCC.
  • The identified circRNA_0023016/EIF4A3/RNF113A/CXCR4 axis represents a novel mechanism in HCC progression.
  • Exosomal circRNA_0023016 holds potential as a therapeutic target for high invasion HCC.

Keywords:
AngiogenesisEndothelial cellsExosomesHepatocellular carcinomacircRNA

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