SREBP-1 has a prognostic role and contributes to invasion and metastasis in human hepatocellular carcinoma

Int J Mol Sci. 2014 Apr 25;15(5):7124-38. doi: 10.3390/ijms15057124.

Abstract

Sterol regulatory element-binding protein 1 (SREBP-1) is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC), is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05). SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM) stage (p < 0.05). The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05). Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05). In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05). Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05). These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver / metabolism
  • Liver / pathology*
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / diagnosis
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Metastasis / diagnosis
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology*
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Sterol Regulatory Element Binding Protein 1 / analysis*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Up-Regulation

Substances

  • RNA, Small Interfering
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1