Transactivation of the human NME5 gene by Sp1 in pancreatic cancer cells

Gene
Fu LiLuyong Zhang

Abstract

Non-metastatic cells 5 (NME5), a recently found gene belonging to the NDPK-like molecules gene family, is highly expressed in testis and some types of human cancer. Current studies have revealed diverse potential functions of NME5 and we have reported that NME5 is associated with innate resistance to gemcitabine in human pancreatic cancer cells in previous study. However, the mechanism underlying the transcriptional regulation of NME5 has not been elucidated yet. In this study, we analyzed the 5'-flanking region of the human NME5 gene and revealed its transcription start site (TSS) at -35 bp relative to its translation start codon ATG. Using 5' unidirectional deletion analysis, we demonstrated that the proximal promoter of NME5 is located within -1051 bp to +35 bp. Two functional GC-boxes (-300 bp and -323 bp) were identified within the promoter region. Mutation of either GC-box led to significant reduction in NME5 promoter activity, whereas overexpression of Sp1 activated NME5 promoter activity in MIA PaCa-2 and 293T cells. In silico analysis predicted that transcription factor Sp1 binds to both GC-boxes, which were confirmed by EMSA and ChIP. In addition, we found that compared with MIA PaCa-2, Sp1 was highly expressed in PAX...Continue Reading

References

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Citations

Jan 10, 2013·PloS One·Jianjun XiongWeidong Li
Feb 20, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·S HeinonenK H Pietiläinen
Apr 15, 2018·Liver International : Official Journal of the International Association for the Study of the Liver·Xinran ZhangYongmei Li
Oct 16, 2016·Oncotarget·Yongli ZhangXiaoping Wan
Oct 31, 2019·Animals : an Open Access Journal From MDPI·Xiaoyang LvJinyu Wang
Dec 28, 2019·Marine Drugs·Dragutin PerinaHelena Ćetković

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