Response gene to complement 32 (RGC32) is a novel cellular protein that has been reported to be expressed aberrantly in multiple types of human tumors. However, the role of RGC32 in cancer is still controversial, and the molecular mechanisms by which RGC32 contributes to the development of cancer remain largely unknown. In the present study, we constructed a recombinant expression vector pCDNA3.1-RGC32 and transfected it into human lung cancer A549 cells. Stable transformanted cells were identified by real-time PCR and Western blot analysis. Functional analysis showed that forced overexpression of RGC32 increased invasive and migration capacities of lung cancer cells in vitro, and induced the acquisition of epithelial–mesenchymal transition (EMT) phenotype, as demonstrated by the spindle-like morphology, downregulation of E-cadherin, and upregulation of Vimentin, Fibronectin, Snail and Slug. Also, overexpression of RGC32 increased expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 in A549 cells. Furthermore, the downregulation of E-cadherin induced by RGC32 was remarkably attenuated by nuclear factor-κB (NF-κB) inhibitor BAY 11-7028 and small interfering RNA targeting NF-κB p65, suggesting a role of the NF-κB signaling pathway in RGC32-induced EMT. Taken together, our data suggest that RGC32 promotes cell migration and invasion and induces EMT in lung cancer cells via the NF-κB signaling pathway.
Response gene to complement 32 Lung cancer Invasion Migration Epithelial–mesenchymal transition Nuclear factor-κB
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Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50. doi:10.1200/JCO.2005.05.2308.CrossRefPubMedGoogle Scholar
Badea TC, Niculescu FI, Soane L, Shin ML, Rus H. Molecular cloning and characterization of RGC-32, a novel gene induced by complement activation in oligodendrocytes. J Biol Chem. 1998;273(41):26977–81.CrossRefPubMedGoogle Scholar
Lorenzl S, Albers DS, Narr S, Chirichigno J, Beal MF. Expression of MMP-2, MMP-9, and MMP-1 and their endogenous counterregulators TIMP-1 and TIMP-2 in postmortem brain tissue of Parkinson’s disease. Exp Neurol. 2002;178(1):13–20.CrossRefPubMedGoogle Scholar
Heissig B, Hattori K, Friedrich M, Rafii S, Werb Z. Angiogenesis: vascular remodeling of the extracellular matrix involves metalloproteinases. Curr Opin Hematol. 2003;10(2):136–41.CrossRefPubMedGoogle Scholar
Zhu L, Qin H, Li PY, Xu SN, Pang HF, Zhao HZ, et al. Response gene to complement-32 enhances metastatic phenotype by mediating transforming growth factor beta-induced epithelial–mesenchymal transition in human pancreatic cancer cell line BxPC-3. J Exp Clin Cancer Res. 2012;31:29. doi:10.1186/1756-9966-31-29.PubMedCentralCrossRefPubMedGoogle Scholar