Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery
Abstract Background Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to f...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Endocrine Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12902-023-01360-z |
| _version_ | 1827943377722671104 |
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| author | Xue Yang Yonglin Wu Shaojie Xu Hanning Li Chengcheng Peng Xiaoqing Cui Deenraj Kush Dhoomun Ge Wang Tao Xu Menglu Dong Xingrui Li Yaying Du |
| author_facet | Xue Yang Yonglin Wu Shaojie Xu Hanning Li Chengcheng Peng Xiaoqing Cui Deenraj Kush Dhoomun Ge Wang Tao Xu Menglu Dong Xingrui Li Yaying Du |
| author_sort | Xue Yang |
| collection | DOAJ |
| description | Abstract Background Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to find a therapeutic target in redifferentiation strategies for thyroid cancer. Methods Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking. Results We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1. Conclusion This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer. |
| first_indexed | 2024-03-13T10:14:29Z |
| format | Article |
| id | doaj.art-4fe7075966614877b26184920de2be73 |
| institution | Directory Open Access Journal |
| issn | 1472-6823 |
| language | English |
| last_indexed | 2024-03-13T10:14:29Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Endocrine Disorders |
| spelling | doaj.art-4fe7075966614877b26184920de2be732023-05-21T11:18:33ZengBMCBMC Endocrine Disorders1472-68232023-05-0123111310.1186/s12902-023-01360-zTargeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discoveryXue Yang0Yonglin Wu1Shaojie Xu2Hanning Li3Chengcheng Peng4Xiaoqing Cui5Deenraj Kush Dhoomun6Ge Wang7Tao Xu8Menglu Dong9Xingrui Li10Yaying Du11Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Huanggang Central HospitalDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to find a therapeutic target in redifferentiation strategies for thyroid cancer. Methods Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking. Results We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1. Conclusion This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer.https://doi.org/10.1186/s12902-023-01360-zDifferentiated papillary thyroid cancerThyroid-stimulating hormone receptorArtificial intelligenceDeep dockingComputer-aided drug discoveryKCNJ16/Kir5.1 |
| spellingShingle | Xue Yang Yonglin Wu Shaojie Xu Hanning Li Chengcheng Peng Xiaoqing Cui Deenraj Kush Dhoomun Ge Wang Tao Xu Menglu Dong Xingrui Li Yaying Du Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery BMC Endocrine Disorders Differentiated papillary thyroid cancer Thyroid-stimulating hormone receptor Artificial intelligence Deep docking Computer-aided drug discovery KCNJ16/Kir5.1 |
| title | Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery |
| title_full | Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery |
| title_fullStr | Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery |
| title_full_unstemmed | Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery |
| title_short | Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery |
| title_sort | targeting the inward rectifier potassium channel 5 1 in thyroid cancer artificial intelligence facilitated molecular docking for drug discovery |
| topic | Differentiated papillary thyroid cancer Thyroid-stimulating hormone receptor Artificial intelligence Deep docking Computer-aided drug discovery KCNJ16/Kir5.1 |
| url | https://doi.org/10.1186/s12902-023-01360-z |
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