SEMA3F Promotes Liver Hepatocellular Carcinoma Metastasis by Activating Focal Adhesion Pathway

DNA Cell Biol. 2020 Mar;39(3):474-483. doi: 10.1089/dna.2019.4904. Epub 2020 Jan 21.

Abstract

Previous studies have shown that semaphorin-3F (SEMA3F) functions as a tumor suppressor in several tumor types. However, the role of SEMA3F in the metastasis and prognosis of liver hepatocellular carcinoma (LIHC) remains unknown. In this study, by performing bioinformatics analysis on the transcriptome profiles from The Cancer Genome Atlas (TCGA), we demonstrated that SEMA3F was significantly upregulated in LIHC tissues, compared with normal controls. Moreover, the expression value of SEMA3F was positively correlated with patients' pathological stages and tumor metastasis, predicting a poor overall survival. Besides, SEMA3F expression level was negatively correlated with its methylation level, but positively correlated with its gene copy number. Differential expression analysis of LIHC samples with high or low SEMA3F expression values suggested that 983 genes were differentially expressed, among which 723 genes were upregulated and 260 genes were downregulated. Furthermore, enrichment analysis of differentially expressed genes revealed that SEMA3F was involved in the activation of focal adhesion pathway, which induced tumor metastasis. Taken together, our results suggested that the oncogenic function of SEMA3F promoted hepatocellular carcinoma metastasis by activating focal adhesion pathway.

Keywords: SEMA3F; focal adhesion pathway; liver hepatocellular carcinoma; metastasis; prognosis.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Metastasis
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SEMA3F protein, human
  • Focal Adhesion Protein-Tyrosine Kinases