A platform for research: civil engineering, architecture and urbanism
A platform for research: civil engineering, architecture and urbanism
Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC
https://orcid.org/0000-0002-6515-6001
AbstractNon‐small‐cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank‐binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417‐AGO2), which promotes NSCLC progression by increasing the formation of microRNA‐induced silencing complex (miRISC). High levels of pS417‐AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417‐AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib‐resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1‐mediated pS417‐AGO2 and suggest potential therapeutic approaches for NSCLC.
Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC
https://orcid.org/0000-0002-6515-6001
AbstractNon‐small‐cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank‐binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417‐AGO2), which promotes NSCLC progression by increasing the formation of microRNA‐induced silencing complex (miRISC). High levels of pS417‐AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417‐AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib‐resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1‐mediated pS417‐AGO2 and suggest potential therapeutic approaches for NSCLC.
Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC
https://orcid.org/0000-0002-6515-6001
AbstractNon‐small‐cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank‐binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417‐AGO2), which promotes NSCLC progression by increasing the formation of microRNA‐induced silencing complex (miRISC). High levels of pS417‐AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417‐AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib‐resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1‐mediated pS417‐AGO2 and suggest potential therapeutic approaches for NSCLC.
Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC
Advanced Science
Zhao, Xian (author) / Cao, Yingting (author) / Lu, Runhui (author) / Zhou, Zihan (author) / Huang, Caihu (author) / Li, Lian (author) / Huang, Jiayi (author) / Chen, Ran (author) / Wang, Yanli (author) / Huang, Jian (author)
Advanced Science ; 11
2024-04-01
Article (Journal)
Electronic Resource
English
Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC
| Wiley | 2024
Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies
| Wiley | 2025
Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies
| Wiley | 2025
Phosphorylation of USP29 by CDK1 Governs TWIST1 Stability and Oncogenic Functions
| Wiley | 2023