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SLIT2 modulates NMIIA to regulate mitophagy and suppress hepatocellular carcinoma progression

Yong Qin1, Junbin Zhou1, Shimiao Li1

  • 1Department of Hepatobiliary Pancreatic Surgery, Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University. Lishui People's Hospital, East of the intersection of National Highway 330 and Liyang Street, Liandu district, Lishui, Zhejiang, 323000, China.

BMC Cancer
|October 14, 2025
PubMed

Insights

Slit guidance ligand 2 (SLIT2) and non-muscle myosin IIA (NMIIA) play key roles in hepatocellular carcinoma (HCC) progression. Targeting the SLIT2/NMIIA axis offers a promising therapeutic strategy for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Hepatocellular carcinoma (HCC) exhibits aggressive progression and metastasis.
  • Complex molecular interactions drive HCC development and spread.

Purpose of the Study:

  • To elucidate the roles of slit guidance ligand 2 (SLIT2) and non-muscle myosin IIA (NMIIA) in HCC.
  • To explore the mechanistic interplay between SLIT2 and NMIIA in HCC progression.

Main Methods:

  • Immunofluorescence and quantitative PCR (Q-PCR) for gene expression analysis.
  • Functional assays to assess cell proliferation, migration, and invasion.
  • In vivo xenograft studies in mice.
  • Analysis of The Cancer Genome Atlas (TCGA) dataset.

Main Results:

  • SLIT2 was significantly downregulated, while NMIIA was upregulated in HCC tissues.
  • SLIT2 expression inversely correlated with tumor stage and metastasis.
  • SLIT2 overexpression inhibited HCC cell growth and metastasis.
  • NMIIA overexpression enhanced HCC cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and mitophagy.
  • SLIT2 suppressed NMIIA activity by inhibiting MRLC phosphorylation.
  • NMIIA enhanced cell adhesion and colony formation.

Conclusions:

  • The SLIT2/NMIIA axis is a critical regulator of HCC progression.
  • SLIT2 acts as a tumor suppressor, while NMIIA promotes oncogenesis in HCC.
  • Targeting the SLIT2/NMIIA pathway presents a potential therapeutic strategy for HCC.
Keywords:
Epithelial-mesenchymal transitionHepatocellular carcinomaMitophagyNon-muscle myosin IIASlit guidance ligand 2

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