Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human
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Published on: August 20, 2019
Gireedhar Venkatachalam1, Alan Prem Kumar, Loo Ser Yue
1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. bchgv@nus.edu.sg
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.
Insights
Peroxisome proliferator-activated receptors (PPARs) show anti-cancer effects. This study identified PPAR binding sites in NHE1 and MnSOD genes, confirming their regulation by PPARs, suggesting potential cancer therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Peroxisome proliferator-activated receptors (PPARs) regulate gene transcription and exhibit anti-proliferative and pro-apoptotic effects on malignant cells.
- PPARs are promising therapeutic targets in cancer treatment due to their regulatory roles in cell growth and death.
Purpose of the Study:
- To computationally identify PPAR response elements (PPREs) in the promoter regions of NHE1 and MnSOD genes.
- To experimentally validate the predicted PPAR binding sites and confirm the regulation of NHE1 and MnSOD by PPARs.
Main Methods:
- Computational analysis to predict PPAR binding regions (PPRE motifs) in NHE1 and MnSOD gene sequences.
- In vitro experiments to validate the identified PPRE motifs and confirm PPAR-mediated gene regulation.
Main Results:
- Computational analysis predicted 2 PPRE motifs in NHE1 and 3 PPRE motifs in MnSOD.
- Experimental validation confirmed the presence of functional PPRE motifs in both genes and demonstrated their regulation by PPARs upon ligand binding.
Conclusions:
- NHE1 and MnSOD genes possess PPRE binding motifs in their upstream/promoter regions.
- These genes are subject to regulation by PPARs following ligand activation, indicating a role in cellular processes relevant to cancer.
