Upregulation of cystatin SN promotes hepatocellular carcinoma progression and predicts a poor prognosis

J Cell Physiol. 2019 Dec;234(12):22623-22634. doi: 10.1002/jcp.28828. Epub 2019 May 20.

Abstract

Cystatin SN, a specific cysteine protease inhibitor, is thought to be involved in various malignant tumors. Therefore, we evaluated the role of cystatin SN in hepatocellular carcinoma (HCC). Notably, cystatin SN was elevated in tumorous samples and cells. Moreover, overexpression of cystatin SN was correlated with tumor diameter and TNM stage. Cox multivariate analysis displayed that cystatin SN was an independent prognosis indicator and that high cystatin SN level was associated with a dismal prognosis. Moreover, cystatin SN enhancement facilitated the proliferation, migratory, and invasive potential of Huh7 and HCCLM3 cells, whereas cystatin SN knockdown caused the opposite effect. Cystatin SN also modulated the epithelial-mesenchymal transition progression through the PI3K/AKT pathway. In vivo cystatin SN promoted HCCLM3 cell growth and metastasis in xenograft mice model. Thus, cystatin SN was involved in HCC progression and could be a latent target for HCC treatment.

Keywords: cell proliferation; cystatin SN; epithelial-mesenchymal transition; hepatocellular carcinoma; prognostic marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Middle Aged
  • Neoplasms, Experimental
  • Phosphatidylinositol 3-Kinases
  • Prognosis
  • Proto-Oncogene Proteins c-akt
  • Salivary Cystatins / genetics
  • Salivary Cystatins / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CST1 protein, human
  • Salivary Cystatins
  • Proto-Oncogene Proteins c-akt