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Published on: August 20, 2019
Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human
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.
