Background: Nucleus accumbens-associated protein 1 (NAC1) has multifaceted roles in cancer pathogenesis and progression, including the development of drug resistance, promotion of cytokinesis, and maintenance of "stem cell-like" phenotypes. NAC1 is a transcriptional co-regulator belonging to the bric-a-brac tramtrack broad (BTB) family of proteins, although it lacks the characteristic DNA binding motif of the BTB family. The formation of higher-order transcription complexes likely depends on its interaction with other DNA-binding co-factors. Results: NAC1 interacts with BCL6 via its C-terminal BEN domain and forms a complex that binds the promoter region and activates transcription of the NAC1 target gene, FOXQ1. NAC1 and BCL6 were coordinately upregulated. Our analysis also identified a novel function of NAC1 in attenuating BCL6 auto-downregulation in ovarian cancer. Lastly, we found a significant overlap among NAC1-and BCL6-regulated genes in tumor cells, suggesting that NAC1 and BCL6 coordinately control transcription in cancer. Conclusions: The results of this study provide a novel mechanistic insight into the oncogenic roles of NAC1 and underline the importance of developing the NAC1/BCL6-targeted cancer therapy. Methods: Using the Cistrome database and Chromatin Immunoprecipitation (ChIP) analyses, we identified BCL6 as a potential NAC1-interacting molecule. Co-immunoprecipitation (Co-IP), luciferase reporter assay, immunohistochemistry and microarray analysis were performed to analyze the interaction between NAC1 and BCL6 and the mechanisms by which they regulate the downstream genes including FOXQ1.
|Number of pages||17|
|State||Published - May 31 2020|
Bibliographical noteFunding Information:
We would like to acknowledge the reviewers for their helpful comments on this paper. This work was supported by National Natural Science Foundation of China (81502245, 81874107 and 81572554); Shandong Provincial Natural Science Foundation (ZR2014HQ016) and the Fundamental Research Funds of Shandong University (2018JC014). A.L.H. is a fellow of Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; process No. 10417/12-5).
© 2020, Gao et al.
ASJC Scopus subject areas
- Cell Biology