miR-301a promotes pancreatic cancer cell proliferation by directly inhibiting Bim expression

J Cell Biochem. 2012 Oct;113(10):3229-35. doi: 10.1002/jcb.24200.

Abstract

It is well known that microRNAs (miRNAs) play an important role in many diseases, including tumorigenesis. However, the mechanisms by which miRNAs regulate pancreatic cancer (PC) development remain poorly understood. In the present study, we assayed expression level of miR-301a in PC tissues by real-time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We first verified that the expression level of miR-301a was significantly increased in PC tissues. Moreover, miR-301a overexpression promoted PC cell proliferation, whereas its depletion decreased cell proliferation. We further demonstrated that miR-301a directly targeted 3'-UTR of Bim gene, and inhibited its protein expression in vitro and in vivo. Importantly, Bim re-expression reduced PC cell proliferation induced by miR-301a. These data suggest an important role of miR-301a in the molecular etiology of PC and implicate the potential application of miR-301a in PC therapy.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Bcl-2-Like Protein 11
  • Blotting, Western
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Humans
  • Luciferases / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Real-Time Polymerase Chain Reaction

Substances

  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • MIRN301A microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Neoplasm
  • Luciferases