Evaluation of transcriptionally regulated genes identifies NCOR1 in hormone receptor negative breast tumors and lung adenocarcinomas as a potential tumor suppressor gene.

Abstract

Regulation of transcription is a key process in cellular homeostasis. It depends on regulators that either repress or stimulate the transcription of genes, therefore controlling different biological functions. The Nuclear Receptor Corepressor 1 (NCOR1) is one of those co-repressors that regulate the transcription by facilitating the recruitment of HDAC1, 2, 3, 4, 5 and 7. In our article, by using an in silico approach, we evaluate the mutational status of NCOR1 in breast and lung tumors. We identified that NORC1 is mutated in more than 3% of breast tumors and lung adenocarcinomas and linked this fact with detrimental outcome in some subtypes, particularly in those that are hormone receptor negative. In addition to these findings, as mutations in this gene are deleterious, we confirmed that high levels of this gene were linked with good prognosis in the same tumor subtypes. Findings in the same direction were identified in lung adenocarcinomas, with mutations associated with detrimental prognosis and high expression with better outcome. In conclusion, hereby we describe the presence and prognostic role of mutations in the NCOR1 gene in hormone receptor negative breast and lung adenocarcinomas, and we also confirm that NCOR1 is a tumor suppressor gene. Further studies should be performed to explore therapeutic mechanisms to restore its function.