计算鉴定和实验验证人类 NHE1 和 MnSOD 基因中的 PPRE 基序。

Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human.

机构信息

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

BMC Genomics. 2009 Dec 3;10 Suppl 3(Suppl 3):S5. doi: 10.1186/1471-2164-10-S3-S5.

BACKGROUND

Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene. Hence, PPARs represent promising targets for cancer treatment because of their anti-proliferative and pro-apoptotic activities. Here we computationally identified PPAR binding regions in NHE1 and MnSOD. We further validated the predictions in vitro.

RESULTS

Our results computationally predicted the presence of 2 PPRE motifs in NHE1 and 3 PPRE motifs in MnSOD. We experimentally confirmed the true motifs and their regulation by PPAR.

CONCLUSION

Our results suggest that both NHE1 and MnSOD have PPRE binding motif in their upstream/promoter region and hence are regulated by PPAR upon ligand binding.

背景

已有研究表明，激活过氧化物酶体增殖物激活受体（PPARs）能够抑制不同谱系的恶性细胞增殖。PPARs 在配体激活后参与基因转录调控。PPAR 与启动子序列的结合会抑制或激活基因。因此，由于其具有抗增殖和促凋亡活性，PPAR 成为癌症治疗的有前途的靶点。在这里，我们通过计算方法鉴定了 NHE1 和 MnSOD 中的 PPAR 结合区域，并在体外进行了验证。