title: Overexpression of response gene to complement 32 (RGC32) promotes cell invasion and induces epithelial-mesenchymal transition in lung cancer cells via the NF-κB signaling pathway.
abstract: 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.
authors.affiliation: Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China.
authors.forename: Qinying
authors.initials: Q
authors.lastname: Sun
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Yao
authors.forename: Yunye
authors.initials: Y
authors.lastname: Ning
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Guowu
authors.initials: G
authors.lastname: Zhou
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Dong
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C498143:RELA protein, human; C115049:RGCC protein, human; D051996:Transcription Factor RelA; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9