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Functional assessment of NF-Kb1 gene in the tumorigenesis of renal cell carcinoma cell lines

Grant number: 14/19265-7
Support type:Regular Research Grants
Duration: August 01, 2015 - July 31, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Maria Helena Bellini Marumo
Grantee:Maria Helena Bellini Marumo
Home Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The renal cell carcinoma (RCC) accounts for approximately 2-3% of human malignancies and, among urologic tumors, it is the most aggressive. The biological heterogeneity, drug resistance and side effects to chemotherapy are the biggest obstacles to effective treatment of RCC. Several molecules have been identified as responsible for the aggressive phenotype of this tumor, one being the NF-:² transcription factor. NF-:² is the collective name for the transcription factors of the Rel family. In mammals, five members of this family are known: RelA (p65), RelB, c-Rel, NF-:²1 (p105/p50) and NF-:²2 (p100 / p52). The functional role of NF-:²1 in the RCC has been investigated in recent years but is far from being elucidated. The nf-kb1 gene encodes the p105 protein which undergoes cleavage and removal of the carboxy-terminal portion of the 26S proteasome, generating the p50 protein that is capable of binding to DNA but lacks transcriptional activity. For this reason, the p50 homodimers are considered inhibitors of transcription. However, these dimers can recruit a co-activator, Bcl-3, and thereby promote the activation of gene transcription. In the last decade several studies have demonstrated the activation of NF-k² in CCR and many pointed to p50 as an important molecule in tumor procession and metastasis. In our recent work we´ve demonstrated, by gel supershift, that p50 was the only member of NF-k² family linked to the DNA of metastatic tumor cells. Furthermore, the p50/Bcl-3 complex was found in the nucleus of tumor cells, indicating an important role of p50 dimers in transcriptional regulation of genes in metastatic RCC. In this study we intend to evaluate the effect of silencing the nfkb1 gene in RCC cell lines using RNA interference technique. Besides, the potential of nfkb1 gene as a therapeutic target will be verified. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TEIXEIRA, LUIZ FELIPE S.; PERON, JEAN PIERRE S.; BELLINI, MARIA HELENA. 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. MOLECULAR BIOLOGY REPORTS, v. 47, n. 2, p. 1143-1151, FEB 2020. Web of Science Citations: 0.
DA SILVA, REGIANE MARINHO; KO, GUI MI; SILVA, RINALDO FLORENCIO; VIEIRA, LUDMILA CABREIRA; DE PAULA, RAFAEL VICENTE; MARUMO, JULIO TAKEHIRO; IKEGAMI, AMANDA; BELLINI, MARIA HELENA. Essential Elements as Biomarkers of Acute Kidney Injury and Spontaneous Reversion. BIOLOGICAL TRACE ELEMENT RESEARCH, v. 182, n. 2, p. 303-308, APR 2018. Web of Science Citations: 1.
IKEGAMI, AMANDA; TEIXEIRA, LUIZ FELIPE S.; BRAGA, MARINA S.; DIAS, MATHEUS HENRIQUE DOS S.; LOPES, EDUARDO C.; BELLINI, MARIA HELENA. Knockdown of NF-kappa B1 by shRNA Inhibits the Growth of Renal Cell Carcinoma In Vitro and In Vivo. ONCOLOGY RESEARCH, v. 26, n. 5, p. 743-751, 2018. Web of Science Citations: 0.

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