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DLC1 as Druggable Target for Specific Subsets of Gastric Cancer: An RNA-seq-Based Study
Lianlei Yang1, Adil Manzoor Bhat2, Sahar Qazi2
1Department of Gastroenterology, The First People's Hospital of Linping District, Hangzhou 311100, China.
Abstract:
Background: Gastric cancer has been ranked the third leading cause of cancer death worldwide. Its detection at the early stage is difficult because patients mostly experience vague and non-specific symptoms in the early stages. Methods: The RNA-seq datasets of both gastric cancer and normal samples were considered and processed. The obtained differentially expressed genes were then subjected to functional enrichment analysis and pathway analysis. An implicit atomistic molecular dynamics simulation was executed on the selected protein receptor for 50 ns. The electrostatics, surface potential, radius of gyration, and macromolecular energy frustration landscape were computed. Results: We obtained a large number of DEGs; most of them were down-regulated, while few were up-regulated. A DAVID analysis showed that most of the genes were prominent in the KEGG and Reactome pathways. The most prominent GAD disease classes were cancer, metabolic, chemdependency, and infection. After an implicit atomistic molecular dynamics simulation, we observed that DLC1 is electrostatically optimized, stable, and has a reliable energy frustration landscape, with only a few maximum energy frustrations in the loop regions. It has a good functional and binding affinity mechanism. Conclusions: Our study revealed that DLC1 could be used as a potential druggable target for specific subsets of gastric cancer.
Insights
This study identifies DLC1 as a potential drug target for gastric cancer. Molecular simulations show DLC1 is stable and has good binding affinity, suggesting its therapeutic potential.
Area of Science:
- Genomics
- Molecular Biology
- Computational Biology
Background:
- Gastric cancer is a leading cause of cancer death globally.
- Early detection is challenging due to vague symptoms.
- Identifying novel therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To identify potential druggable targets for gastric cancer.
- To investigate the molecular characteristics of candidate targets using computational methods.
Main Methods:
- RNA sequencing (RNA-seq) data analysis to identify differentially expressed genes (DEGs) in gastric cancer.
- Functional enrichment and pathway analysis (DAVID, KEGG, Reactome).
- Implicit atomistic molecular dynamics simulations to assess protein stability and binding affinity.
Main Results:
- A significant number of DEGs were identified, with most showing down-regulation.
- Enrichment analysis highlighted key pathways and disease classes, including cancer.
- Molecular dynamics simulations indicated DLC1 is a stable protein with favorable functional and binding properties.
Conclusions:
- DLC1 demonstrates potential as a druggable target for specific gastric cancer subtypes.
- Further research into DLC1-targeted therapies may offer new treatment avenues.
- Computational approaches are valuable for identifying and validating therapeutic targets in cancer.
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