Aberrant expression miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells

Pancreas. 2013 Oct;42(7):1169-81. doi: 10.1097/MPA.0b013e3182962acb.

Abstract

Objectives: MiR-196a levels inversely correlated with survival in pancreatic adenocarcinoma patients. However, the functional contributions of miR-196a to pancreatic cancer remain unclear.

Methods: Three lentiviral vectors encoding microRNA miR-196a precursor, inhibitor, and scrambled microRNA oligomer were transfected into Panc-1 cells, respectively. Then we explored the regulation of inhibitor of growth 5 (ING5) expression by miR-196a and its impact on apoptosis, invasion, and growth of pancreatic cancer cells. The lentiviral transfected Panc-1 cells were surgically implanted into the pancreas of mice. In vivo tumor growth and ING5 expression were measured.

Results: Down-regulation of ING5 expression was detected in cells transfected with miR-196a precursor (P < 0.01), accompanied by less apoptosis, increased invasion, and proliferation compared with control cells (P < 0.05). Cells transfected with miR-196a inhibitor revealed an opposite trend. Smaller detectable tumors were found in only 60% of mice after implantation of Lenti.miR-196a inhibitor-transfected Panc-1 cells compared with controls (360.7 ± 303.6 mm vs 511.58 ± 365.9 mm in controls; P < 0.01).

Conclusion: Our results provide experimental evidence to support aberrant expression of miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • 3' Untranslated Regions
  • ING5 protein, human
  • MIRN196 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • Transcription Factors
  • Tumor Suppressor Proteins