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

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Tumor Biology

An Erratum to this article was published on 10 December 2014

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.

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Authors and Affiliations

  1. Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People’s Republic of China

    Huiyan Niu, Baogang Wu, Yang Peng, Hongfang Jiang, Yi Zhang, Jiahe Wang, Yifei Zhang & Ping He

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  1. Huiyan Niu
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  2. Baogang Wu
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  3. Yang Peng
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  4. Hongfang Jiang
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  5. Yi Zhang
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  6. Jiahe Wang
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  7. Yifei Zhang
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  8. Ping He
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Correspondence to Ping He.

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An erratum to this article is available at http://dx.doi.org/10.1007/s13277-014-2904-y.

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Niu, H., Wu, B., Peng, Y. et al. RNA interference-mediated knockdown of RhoGDI2 induces the migration and invasion of human lung cancer A549 cells via activating the PI3K/Akt pathway. Tumor Biol. 36, 409–419 (2015). https://doi.org/10.1007/s13277-014-2671-9

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  • DOI: https://doi.org/10.1007/s13277-014-2671-9

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