Hic-5 in pancreatic stellate cells affects proliferation, apoptosis, migration, invasion of pancreatic cancer cells and postoperative survival time of pancreatic cancer

Biomed Pharmacother. 2020 Jan:121:109355. doi: 10.1016/j.biopha.2019.109355. Epub 2019 Nov 1.

Abstract

Pancreatic cancer is one of the most severe types of tumors, with a 5-year survival rate of less than 7%. The prognosis and treatment of pancreatic cancer are largely limited by the extent of tumor invasion and the presence of lymph node and distant metastases. Therefore, exploring the biological behavior of pancreatic cancer cells (PCCs) is extremely important for the understanding, diagnosis, and treatment of pancreatic cancer. Current studies have shown that pancreatic stellate cells (PSCs) regulate the biological behavior of PCCs, such as their proliferation, apoptosis, invasion, and migration, by remodeling the extracellular matrix. Though Hic-5 is an important gene in PSCs, no study has investigated the regulation of PCCs by Hic-5. Here, we demonstrate that Hic-5 expression is upregulated in pancreatic cancer and that siRNA transfection can effectively inhibit Hic-5 expression. Compared to the control group, Hic-5 inhibition significantly reduced proliferation, increased apoptosis, and reduced invasion and migration of PCCs. Moreover, the inhibition of Hic-5 expression simultaneously reduced matrix metalloproteinase-9 (MMP-9) expression. Statistical analysis revealed that Hic-5 expression was higher among the pancreatic cancer group than among the normal group and was negatively correlated with postoperative survival time among patients with pancreatic cancer. These results have important clinical significance for further exploring the molecular mechanism involved in Hic-5-mediated invasion and metastasis of pancreatic cancer and ameliorating the prognosis of patients with pancreatic cancer.

Keywords: Apoptosis; Hic-5; Invasion and migration; Pancreatic cancer; Pancreatic stellate cells; Proliferation; Survival time.

MeSH terms

  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Coculture Techniques / methods
  • Extracellular Matrix / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • LIM Domain Proteins / genetics*
  • Matrix Metalloproteinase 9 / genetics
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Pancreas / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Stellate Cells / pathology*
  • Prognosis
  • RNA, Small Interfering / genetics
  • Up-Regulation / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • RNA, Small Interfering
  • TGFB1I1 protein, human
  • Matrix Metalloproteinase 9