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Endoplasmic reticulum stress-related CLIP4 plays a procarcinogenic role in hepatocellular carcinoma: an integrated

Anqi Wang1, Sitong Yan1,2, Weijia Jiang1

  • 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui Province, 230022, China.

BMC Cancer
|February 7, 2025
PubMed
Abstract

Insights

Endoplasmic reticulum stress (ERS)-associated protein CLIP4 promotes hepatocellular carcinoma (HCC) progression by enhancing proliferation, migration, and epithelial-mesenchymal transition (EMT). CLIP4 is a potential immune-related oncogenic biomarker in HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective biomarkers.
  • Endoplasmic reticulum stress (ERS) is increasingly recognized for its role in cancer development and progression.
  • CLIP4, an ERS-associated protein, has an uncharacterized role in HCC pathogenesis.

Purpose of the Study:

  • To investigate CLIP4 as a potential biomarker for HCC.
  • To elucidate the underlying mechanisms by which CLIP4 influences HCC progression.
  • To explore the regulatory network involving ERS, CLIP4, and its impact on HCC.

Main Methods:

  • Utilized TCGA public database and tissue microarrays for molecular and prognostic analyses of CLIP4 in HCC.
  • Performed gene expression, correlation, enrichment, immune infiltration, and DNA methylation analyses.
  • Employed cell-based assays (CCK-8, colony formation, EdU, wound-healing, Transwell) and molecular techniques (RNA-seq, IHC, Western blot, RT-qPCR) to assess CLIP4 function and regulation.

Main Results:

  • Elevated CLIP4 expression correlated with poor HCC prognosis and was linked to immune response, cell adhesion, and EMT.
  • CLIP4 expression positively correlated with immune cell infiltration and associated molecules.
  • ERS significantly upregulated CLIP4 expression, and a regulatory network (ERS-RELA-miR-222-5p-CLIP4) was identified.
  • CLIP4 was confirmed to promote HCC cell proliferation, migration, and EMT.

Conclusions:

  • CLIP4 functions as an immune-related oncogenic molecule in HCC.
  • ERS-mediated regulation of CLIP4 contributes to HCC progression.
  • CLIP4 promotes HCC cell proliferation, migration, and EMT, highlighting its potential as a therapeutic target.
Keywords:
Bioinformatics analysisCLIP4Endoplasmic reticulum stressEpithelial-mesenchymal transitionHepatocellular carcinoma

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