Tumor Biology

, Volume 33, Issue 6, pp 1863–1870

miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway

  • Yongjun Hu
  • Yanglu Ou
  • Kemin Wu
  • Yuxiang Chen
  • Weijia Sun
Research Article

DOI: 10.1007/s13277-012-0446-8

Cite this article as:
Hu, Y., Ou, Y., Wu, K. et al. Tumor Biol. (2012) 33: 1863. doi:10.1007/s13277-012-0446-8

Abstract

Pancreatic cancer is characterized by early metastasis and high mortality. In this study, the role of miR-143 in invasion and metastasis was investigated in pancreatic cancer cells. miR-143 expression was established by an adenovirus-carried miR-143 expression cassette. mRNA and protein levels of gene expression were examined by RT-PCR and Western blot assay, respectively. Rho GTPases activity was measured by the pull down assay. The role of miR-143 in migration and invasion of Panc-1 cells was tested in vitro. The antimetastatic effect of miR-143 was tested in a liver metastasis model, while its antitumor growth effect was tested in a xenograft Panc-1 tumor model. Results demonstrated that ARHGEF1 (GEF1), ARHGEF2 (GEF2), and K-RAS genes are the targets of miR-143. miR-143 expression significantly decreased mRNA and protein levels of GEF1, GEF2, and K-RAS genes; lowered the constitutive activities of RhoA, Rac1, and Cdc42 GTPases; decreased the protein levels of MMP-2 and MMP-9; but significantly increased the protein level of E-cadherin. miR-143 expression also significantly inhibited the migration and invasion of Panc-1 cells in vitro, liver metastasis, and xenograft tumor growth in vivo. Our study suggested that miR-143 plays a central role in the invasion and metastasis of pancreatic cancer and miR-143 is a potential target for pancreatic cancer therapy.

Keywords

microRNAmiR-143Rho GTPaseGEFE-cadherinPancreatic cancer

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Yongjun Hu
    • 1
  • Yanglu Ou
    • 1
  • Kemin Wu
    • 1
  • Yuxiang Chen
    • 2
  • Weijia Sun
    • 1
  1. 1.Department of General Surgery, Xiangya HospitalCentral South UniversityChangshaPR China
  2. 2.Hepatobiliary and Enteric Surgery Research Center, Xiangya HospitalCentral South UniversityChangshaPR China