miR-16 targets fibroblast growth factor 2 to inhibit NPC cell proliferation and invasion via PI3K/AKT and MAPK signaling pathways

Oncotarget. 2016 Jan 19;7(3):3047-58. doi: 10.18632/oncotarget.6504.

Abstract

Dysregulation of miRNAs has been shown to contribute to the carcinogenesis and progression of nasopharyngeal carcinoma (NPC). Our previous microarray data showed that miR-16 expression is significantly decreased in archived NPC tissues. Here, we confirmed that miR-16 was reduced in NPC cell lines and freshly-frozen samples. Ectopic expression of miR-16 suppressed NPC cell proliferation, migration, and invasion in vitro and inhibited tumor growth and metastatic colonization in the lung in vivo. Furthermore, fibroblast growth factor 2 (FGF2) was identified as a direct target of miR-16, and both phosphoinositide-3- kinase/AKT (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways were repressed after miR-16 overexpression. In addition, the restoration of FGF2 reversed the suppressive effects of miR-16. Together, these results indicated that miR-16 suppresses NPC carcinogenesis and progression by targeting FGF2, thereby representing a potential target for miRNA-based therapy for NPC in the future.

Keywords: fibroblast growth factor 2; metastasis; miR-16; nasopharyngeal carcinoma; tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Fibroblast Growth Factor 2 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • MAP Kinase Signaling System / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinases / genetics*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Recurrence, Local / pathology
  • Phosphatidylinositol 3-Kinases / genetics*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN16 microRNA, human
  • MicroRNAs
  • Fibroblast Growth Factor 2
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases