Research On The Regulation Of C-Myc/NFκB/AP1 To The Promoter Activity Of C1orf109

It is important to study the structure and function of cancer genes, understand the molecular mechanisms of cancer occurrence and development, and find effective treatment of cancer. c1orf109 gene was a new gene which was found in our previous study, its structure and function was unknown. The expresseion of c1orf109 in many tumor tissues was higher than that in normal tissues. It was located at 1p34.3. In this paper, we study the transcription factors which combined with c1orf109 promoter, to comfirm the molecular mechanisms of c1orf109 high expression in tumor cells, based on the previous studies.First, using bioinformatic methods to analyze the mutation and expression of c1orf109 in cancer, and predict potential transcription factor binding sites in c1orf109 proximal promoter, to acquire target transcription factors, and then we built the pcDNA3.1 expression recombinant of c-Myc, NFκB-p65 and AP1-Jun. Second, studying the regulation of c-Myc, NFκB-p65, AP1-Jun to c1orf109 promoter, using the luciferase reporter assay, overexpression and siRNA interference technique. Finally, studying the binding of transcription factor to c1orf109 proximal promoter region, using chromatin immunoprecipitation(ChIP) method, thus confirming the regulatory effect of transcription factor to the promoter.The results indicated that, c1orf109 showed no significant mutations in cancer, and was highly expressed in various tumor tissues. c1orf109 had multiple transcripts, its promoter regions were mainly concentrated in two regions, the distal promoter and proximal promoter. The activity of proximal promoter was much higher than that of distal promoter, core region of proximal promoter lied in-1 ~-177 bp. Transcription factor c-Myc had a positive regulation on c1orf109 proximal promoter, and directly bind to the core region of c1orf109 proximal promoter in-94 bp ~-8 bp sites. Transcription factor NFκB-p65 and AP1-Jun showed no significant regulation on c1orf109 proximal promoter.In summary, this paper explored the molecular mechanisms of c1orf109 high expression in cancer, confirming that the transcription factor c-Myc positively regulated c1orf109 proximal promoter. The study showed a direct combination of both, and confirmed the specific binding region, indicating that c-Myc directly bind to c1orf109 gene promoter, thereby enhancing its transcriptional activity and activing its expression.