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Published on: September 19, 2018
Identification of TNIK as a novel potential drug target in thyroid cancer based on protein druggability prediction
Yi-Fei Yang1, Bin Yu, Xiu-Xia Zhang
1Department of Thyroid and Breast Surgery, The First People's Hospital of Yuhang, Hangzhou, Zhejiang, China.
Abstract:
Thyroid cancer is a common endocrine malignancy; however, surgery remains its primary treatment option. A novel targeted drug for the development and application of targeted therapy in thyroid cancer treatment remain underexplored.We obtained RNA sequence data of thyroid cancer from The Cancer Genome Atlas database and identified differentially expressed genes (DEGs). Then, we constructed co-expression network with DEGs and combined it with differentially methylation analysis to screen the key genes in thyroid cancer. PockDrug-Server, an online tool, was applied to predict the druggability of the key genes. Finally, we constructed protein-protein interaction (PPI) network to observe potential targeted drugs for thyroid cancer.We identified 3 genes correlated with altered DNA methylation level and oncogenesis of thyroid cancer. According to the druggable analysis and PPI network, we predicted TRAF2 and NCK-interacting protein kinase (TNIK) sever as the drug targeted for thyroid cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that genes in protein-protein interaction network of TNIK enriched in mitogen-activated protein kinase signaling pathway. For drug repositioning, we identified a targeted drug of genes in PPI network.Our study provides a bioinformatics method for screening drug targets and provides a theoretical basis for thyroid cancer targeted therapy.
Insights
This study identifies novel drug targets, TRAF2 and TNIK, for thyroid cancer using bioinformatics. These findings offer a new theoretical basis for developing targeted therapies against this common endocrine malignancy.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Thyroid cancer is a prevalent endocrine malignancy, with surgery as the main treatment.
- Targeted drug development for thyroid cancer remains an underexplored area.
Purpose of the Study:
- To identify novel drug targets for thyroid cancer using bioinformatics analysis.
- To provide a theoretical foundation for targeted therapy in thyroid cancer treatment.
Main Methods:
- Analyzed RNA sequencing data from The Cancer Genome Atlas to identify differentially expressed genes (DEGs).
- Constructed co-expression and protein-protein interaction (PPI) networks.
- Performed differential methylation analysis and druggability prediction using PockDrug-Server.
Main Results:
- Identified 3 key genes associated with thyroid cancer oncogenesis and DNA methylation.
- Predicted TRAF2 and TNIK as potential drug targets.
- TNIK's PPI network genes were enriched in the mitogen-activated protein kinase signaling pathway.
Conclusions:
- Developed a bioinformatics approach for screening drug targets in thyroid cancer.
- Identified TRAF2 and TNIK as promising targets for future thyroid cancer targeted therapies.
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