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Identification of small molecule inhibitors for differentially expressed miRNAs in gastric cancer
Dhayalan Pavithra1, Kesavan Sabitha1, Thangarajan Rajkumar1
1Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai, 600036, India.
Abstract:
Gastric cancer is a common cancer in the world with higher incidence rates. Micro RNAs (miRNAs) are known to control biological processes and are also involved in the initiation and progression of numerous cancers. The aim of this study was to identify small molecule inhibitors using bioinformatics methods for over-expressed miRNAs that are known to play a major role in the genesis of gastric cancer. Our study included three datasets from Gene expression omnibus (GEO) database and we used bioinformatics tool to identify differentially expressed miRNAs in all the three datasets. Gene ontology and pathway enrichment analysis of the experimentally validated miRNA target genes and their linkage to oncogenesis were analyzed. Target genes thus identified were found to be linked with the major pathways of cancer. We were interested in identifying small molecules which are specific to over-expressed miRNAs which can arrest oncogenesis. Thus, the computer aided high throughput virtual screening was carried out to identify potent small molecules for over expressed miRNAs in gastric cancer using Glide. Based on docking score top five ligands specific for each miRNAs were identified.
Insights
This study identified potential small molecule inhibitors for over-expressed microRNAs (miRNAs) driving gastric cancer. Bioinformatics analysis pinpointed key miRNAs and their targets, leading to virtual screening for novel therapeutic compounds to halt cancer progression.
Area of Science:
- Oncology
- Bioinformatics
- Molecular Biology
Background:
- Gastric cancer is a prevalent malignancy with significant global incidence.
- MicroRNAs (miRNAs) are crucial regulators of biological processes, implicated in cancer initiation and progression.
- Identifying therapeutic targets for gastric cancer, particularly those involving dysregulated miRNAs, is a critical research area.
Purpose of the Study:
- To identify over-expressed microRNAs (miRNAs) involved in gastric cancer genesis using bioinformatics.
- To discover specific small molecule inhibitors for these over-expressed miRNAs to potentially arrest oncogenesis.
- To analyze the role of miRNA target genes in cancer-related pathways.
Main Methods:
- Utilized three datasets from the Gene Expression Omnibus (GEO) database to identify differentially expressed miRNAs.
- Performed Gene Ontology and pathway enrichment analysis on experimentally validated miRNA target genes.
- Conducted computer-aided high-throughput virtual screening using Glide to identify small molecule inhibitors for over-expressed miRNAs.
Main Results:
- Identified differentially expressed miRNAs across three independent gastric cancer datasets.
- Confirmed that target genes of these miRNAs are linked to major cancer-associated pathways.
- Successfully identified top five potent small molecule ligands for each over-expressed miRNA based on docking scores.
Conclusions:
- Bioinformatics approaches can effectively identify key miRNAs and their targets in gastric cancer.
- The identified small molecules show potential as specific inhibitors for over-expressed miRNAs in gastric cancer.
- This study provides a foundation for developing novel targeted therapies against gastric cancer by modulating miRNA activity.
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