Background. The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of KEAP1 and NFE2L2 genes and KEAP1 promoter hypermethylation, but these two genes have been rarely investigated in low/intermediate grade neuroendocrine tumors of the lung. Methods. The effects of KEAP1 silencing on NRF2 activity was investigated in H720 and H727 carcinoid cell lines and results were compared with those obtained by molecular profiling of KEAP1 and NFE2L2 in a collection of 47 lung carcinoids. The correlation between methylation and transcript levels was assessed by 5-aza-dC treatment. Results. We demonstrated that in carcinoid cell lines, the KEAP1 silencing induces an upregulation of.

Effects of KEAP1 silencing on the regulation of NRF2 activity in neuroendocrine lung tumors

Di Maio M.;Maiello E.;Muscarella L. A.
2019

Abstract

Background. The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of KEAP1 and NFE2L2 genes and KEAP1 promoter hypermethylation, but these two genes have been rarely investigated in low/intermediate grade neuroendocrine tumors of the lung. Methods. The effects of KEAP1 silencing on NRF2 activity was investigated in H720 and H727 carcinoid cell lines and results were compared with those obtained by molecular profiling of KEAP1 and NFE2L2 in a collection of 47 lung carcinoids. The correlation between methylation and transcript levels was assessed by 5-aza-dC treatment. Results. We demonstrated that in carcinoid cell lines, the KEAP1 silencing induces an upregulation of.
20
10
2531
2548
https://www.mdpi.com/1422-0067/20/10/2531/pdf
KEAP1; Lung Carcinoid; NRF2; methylation; mutation; outcome; Adult; Cell Line, Tumor; DNA Methylation; Female; Humans; Kelch-Like ECH-Associated Protein 1; Lung Neoplasms; Male; Middle Aged; NF-E2-Related Factor 2; Neuroendocrine Tumors; Young Adult; Gene Expression Regulation, Neoplastic
Sparaneo A.; Fabrizio F.P.; la Torre A.; Graziano P.; Di Maio M.; Fontana A.; Bisceglia M.; Rossi A.; Pizzolitto S.; De Maglio G.; Tancredi A.; Grimaldi F.; Balsamo T.; Centra F.; Manzorra M.C.; Trombetta D.; Pantalone A.; Bonfitto A.; Maiello E.; Fazio V.M.; Muscarella L.A.
File in questo prodotto:
File Dimensione Formato  
ijms-20-02531.pdf

accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 3.21 MB
Formato Adobe PDF
3.21 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1729974
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact