Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
BMC Genomics. 2009 Dec 3;10 Suppl 3(Suppl 3):S5. doi: 10.1186/1471-2164-10-S3-S5.
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.
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.
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.
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。
我们的计算结果预测了 NHE1 中存在 2 个 PPRE 基序，MnSOD 中存在 3 个 PPRE 基序。我们通过实验证实了这些基序及其受 PPAR 调控的真实性。
我们的结果表明，NHE1 和 MnSOD 的上游/启动子区域都存在 PPRE 结合基序，因此在配体结合时受 PPAR 调控。
