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Tumor Biology

, Volume 36, Issue 1, pp 409–419 | Cite as

RNA interference-mediated knockdown of RhoGDI2 induces the migration and invasion of human lung cancer A549 cells via activating the PI3K/Akt pathway

  • Huiyan Niu
  • Baogang Wu
  • Yang Peng
  • Hongfang Jiang
  • Yi Zhang
  • Jiahe Wang
  • Yifei Zhang
  • Ping He
Research Article

Abstract

Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a tumor suppressor gene for cellular migration and invasion. However, the underlying mechanism and effector targets of RhoGDI2 in lung cancer are still not fully understood. In this study, a vector-expressed small hairpin RNA (shRNA) of RhoGDI2 was transfected into the human lung cancer cell line A549. After the successful transfection, the down-regulation of RhoGDI2 promoted the proliferation, migration, and invasion of lung cancer cells in vitro through the increasing expression and activities of the matrix metallopeptidase 9 (MMP-9) and PI3K/Akt pathways. Transiently transfecting the small interfering RNA (siRNA) of MMP-9 into the RhoGDI2 shRNA cells reduced the MMP-9 expression. Both transfecting the siRNA and adding the MMP-9 antibody into the RhoGDI2 shRNA cells led to a decrease in the invasion and migration of the lung cancer cells. The blockade of the PI3K/Akt pathway by LY294002 resulted in abolishment of the effects of RhoGDI2 shRNA in Akt phosphorylation and MMP-9 expression. This result suggests that the down-regulated RhoGDI2 contributed to the migration and invasion of the lung cancer cell line via activating the PI3K/Akt pathway and the ensuing increase in the expression and activity of MMP-9. In conclusion, we report that the shRNA-mediated knockdown of RhoGDI2 induces the invasion and migration of lung cancer due to cross-talk with the PI3K/Akt pathway and MMP-9. Verifying the role and molecular mechanism of the participation of RhoGDI2 in the migration and invasion of lung cancer may provide a target for better treatment.

Keywords

RhoGDI2 Lung cancer Metastasis MMP-9 PI3K/Akt 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Huiyan Niu
    • 1
  • Baogang Wu
    • 1
  • Yang Peng
    • 1
  • Hongfang Jiang
    • 1
  • Yi Zhang
    • 1
  • Jiahe Wang
    • 1
  • Yifei Zhang
    • 1
  • Ping He
    • 1
  1. 1.Department of GeriatricsShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China

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