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Updated: Jul 4, 2025

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
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Downregulation of Roundabout guidance receptor 2 suppresses hepatocellular carcinoma progression by interacting with

Ting Liu1, Congjie Zhai2, Bo Tian1

  • 1Department of Endoscopy Center, The First Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang, 050031, Hebei, China.

Scientific Reports
|January 31, 2024
PubMed

Insights

Roundabout guidance receptor 2 (Robo2) is upregulated in hepatocellular carcinoma (HCC). Inhibiting Robo2 suppresses tumor growth and EMT by regulating YB-1, offering a new HCC treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Roundabout guidance receptor 2 (Robo2) is linked to various cancers, but its role in hepatocellular carcinoma (HCC) remains unexplored.
  • Understanding Robo2's function in HCC is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role and mechanism of Robo2 in HCC.
  • To identify Robo2's downstream targets and their involvement in HCC progression.

Main Methods:

  • Robo2 protein levels were measured in HCC and adjacent normal tissues.
  • Robo2 knockdown was performed in HepG2 and Huh7 cell lines using lentiviral vectors.
  • Epithelial-mesenchymal transition (EMT), proliferation, and apoptosis were assessed using western blot, flow cytometry, wound healing, and TUNEL assays.
  • Interactions were verified via Co-IP and immunofluorescence; rescue studies explored the Robo2-YB-1 mechanism.

Main Results:

  • Robo2 expression was significantly higher in HCC tissues compared to normal tissues.
  • Robo2 knockdown suppressed EMT and proliferation while enhancing apoptosis in HCC cells.
  • YB-1 was identified as a downstream target of Robo2.
  • YB-1 overexpression reversed the effects of Robo2 knockdown on apoptosis, EMT, and proliferation.

Conclusions:

  • Robo2 deficiency inhibits HCC progression by suppressing EMT and proliferation and augmenting apoptosis through YB-1 regulation.
  • Targeting Robo2 presents a potential new therapeutic avenue for HCC treatment.

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