Silencing of nuclear factor kappa b 1 gene expression inhibits colony formation, cell migration and invasion via the downregulation of interleukin 1 beta and matrix metallopeptidase 9 in renal cell carcinoma

Autor(es)

Teixeira, Luiz Felipe S. ^[1] ; Peron, Jean Pierre S. ^[2] ; Bellini, Maria Helena ^[1]

Afiliação do(s) autor(es)

^[1] IPEN CNEN SP, Dept Biotechnol, 2242 Ave Lineu Prestes, Cidade Univ, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Immunol, ICB 4, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BIOLOGY REPORTS; v. 47, n. 2, p. 1143-1151, FEB 2020.
• Citações Web of Science: 0

Resumo

Renal cell carcinoma (RCC) is a highly deadly urological tumor due to its high metastatic incidence and its notorious chemoresistance. The nuclear transcription factor kappa B (NF-kappa B) family has been associated with apoptosis resistance and cellular invasion in RCC. The purpose of this study was to evaluate the impact of NF-kappa B1 gene silencing on the colony formation, cell migration and invasion abilities of the RCC cell line. Renca-mock and Renca-shRNA-NF-kappa B1 cells were used in this work. NF-kappa B1 downregulation was assessed by western blotting. The mRNA expression levels of interleukin-1 beta (IL-1 beta) and MMP-9 were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). The IL-1 beta levels in the culture media were determined by a commercial ELISA kit. The MMP-9 protein expression and gelatinolytic activity were evaluated by western blotting and zymography, respectively, and the migration and invasion abilities were analysed. The expression levels of p105 and p50 in Renca-shRNA-NF-kappa Bmoc1 cells were significantly reduced compared with those in the Renca-mock cells. The colony numbers of shRNA-NF-kB1 cells were lower than the colony numbers of the Renca-mock cells. NF-kappa B1 knockdown inhibited the cell migration and invasion of Renca-shRNA-NF-kappa B1 cells. These cells also exhibited reduced levels of IL-1 beta. The MMP-9 expression and activity levels were significantly reduced in Renca-shRNA-NF-kappa B1 cells. Taken together, these results indicate that the downregulation of NF-kappa B1 suppresses the tumourigenicity of RCC by reducing MMP-9 expression and activity; thus, NF-kappa B1 could be a molecular target for RCC treatment. (AU)

• Processo FAPESP: 14/19265-7 - Avaliação funcional do gene NF-Kb1 na tumorigênese de linhagens celulares de carcinoma renal
• Beneficiário: Maria Helena Bellini Marumo
• Modalidade de apoio: Auxílio à Pesquisa - Regular