MicroRNA-195 inhibits the proliferation and invasion of pancreatic cancer cells by targeting the fatty acid synthase/Wnt signaling pathway

Tumour Biol. 2017 Jun;39(6):1010428317711324. doi: 10.1177/1010428317711324.

Abstract

Emerging evidence suggests that microRNAs are critical regulators of cancer development and progression. MicroRNA-195 has been reported as a cancer-related microRNA in many human cancers. However, the role of microRNA-195 in pancreatic cancer remains largely unknown. Here, we show that microRNA-195 is downregulated in pancreatic cancer tissues and cell line. Also, we show that overexpression of microRNA-195 inhibits the proliferation and invasion of pancreatic cancer cells, whereas suppression of microRNA-195 promotes proliferation and invasion. We show that microRNA-195 directly targets the fatty acid synthase enzyme and negatively regulates the expression of fatty acid synthase. Also, we show that fatty acid synthase expression is inversely correlated with microRNA-195 expression in pancreatic cancer tissues. Moreover, our results show that microRNA-195 inhibits Wnt signaling in pancreatic cancer cells. By restoring fatty acid synthase expression, we were able to reverse the antitumor effects of microRNA-195 in pancreatic cancer cells. Taken together, our findings show that microRNA-195 inhibits pancreatic cancer cell proliferation and invasion by regulating the fatty acid synthase/Wnt signaling pathway, suggesting a tumor suppressive role for microRNA-195 in the development and progression of pancreatic cancer. Thus, inhibiting fatty acid synthase by microRNA-195 may serve as a novel therapeutic approach for the treatment of pancreatic cancer.

Keywords: Fatty acid synthase; Wnt; microRNA-195; pancreatic cancer; proliferation.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics*
  • Fatty Acid Synthase, Type I / biosynthesis
  • Fatty Acid Synthase, Type I / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics

Substances

  • MIRN195 microRNA, human
  • MicroRNAs
  • beta Catenin
  • FASN protein, human
  • Fatty Acid Synthase, Type I