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.

TNFα Enhances Tamoxifen Sensitivity through Dissociation of ERα-p53-NCOR1 Complexes in ERα-Positive Breast Cancer

“…Thus, we hypothesized that NCOR1 is associated with the specific antitumor effect of TNFα. Indeed, the role of NCOR1 in cell proliferation and cancer development has been described in previous reports [ 39 , 40 , 41 , 42 ], and our data showed that NCOR1 knockdown selectively suppressed the proliferation of ERα-positive cells in vitro and tumor growth in vivo. Consistently with the specific pro-proliferative function of NCOR1, NCOR1 knockdown induced apoptosis selectively in ERα-positive but not in ERα-negative breast cancer cells.…”

Potential application of genomic profiling for the diagnosis and treatment of patients with sarcoma

“…NCOR1 is a transcription factor that regulates various biological functions ( 61 ). As a tumor suppressor gene, mutation in NCOR1 was confirmed to be associated with the prognostic prediction of numerous cancers, such as breast cancer, lung adenocarcinoma and GISTs ( 62 , 63 ). These findings suggest that NCOR1 mutations are a potential biomarker for the molecular diagnosis and prognosis of osteosarcoma.…”

Effect of NCOR1 Mutations on Immune Microenvironment and Efficacy of Immune Checkpoint Inhibitors in Patient with Bladder Cancer

“…Thus, the difference between the proportion of stage IV patients may contribute to the difference in the KM analysis. Mutations or deletions of NCOR1 have been described in bladder cancer ( 30 ). Thus, deep deletions of NCOR1 have been taken into account.…”