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T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma

T‐lymphokine‐activated killer (T‐LAK) cell‐originated protein kinase (TOPK) is an emerging target with critical roles in various cancers; however, its expression and function in osteosarcoma remain unexplored. We evaluated TOPK expression using RNA sequencing and gene expression data from public dat...

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Autores principales: Thanindratarn, Pichaya, Wei, Ran, Dean, Dylan C., Singh, Arun, Federman, Noah, Nelson, Scott D., Hornicek, Francis J., Duan, Zhenfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637563/
https://www.ncbi.nlm.nih.gov/pubmed/34115928
http://dx.doi.org/10.1002/1878-0261.13039
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author Thanindratarn, Pichaya
Wei, Ran
Dean, Dylan C.
Singh, Arun
Federman, Noah
Nelson, Scott D.
Hornicek, Francis J.
Duan, Zhenfeng
author_facet Thanindratarn, Pichaya
Wei, Ran
Dean, Dylan C.
Singh, Arun
Federman, Noah
Nelson, Scott D.
Hornicek, Francis J.
Duan, Zhenfeng
author_sort Thanindratarn, Pichaya
collection PubMed
description T‐lymphokine‐activated killer (T‐LAK) cell‐originated protein kinase (TOPK) is an emerging target with critical roles in various cancers; however, its expression and function in osteosarcoma remain unexplored. We evaluated TOPK expression using RNA sequencing and gene expression data from public databases (TARGET‐OS, CCLE, GTEx, and GENT2) and immunohistochemistry in an osteosarcoma tissue microarray (TMA). TOPK gene expression was significantly higher in osteosarcoma than normal tissues and directly correlated with shorter overall survival. TOPK was overexpressed in 83.3% of the osteosarcoma specimens within our TMA and all osteosarcoma cell lines, whereas normal osteoblast cells had no aberrant expression. High expression of TOPK associated with metastasis, disease status, and shorter overall survival. Silencing of TOPK with small interfering RNA (siRNA) decreased cell viability, and inhibition with the selective inhibitor OTS514 suppressed osteosarcoma cell proliferation, migration, colony‐forming ability, and spheroid growth. Enhanced chemotherapeutic sensitivity and a synergistic effect were also observed with the combination of OTS514 and either doxorubicin or cisplatin in osteosarcoma cell lines. Taken together, our study demonstrated that TOPK is a potential prognostic biomarker and therapeutic target for osteosarcoma treatment.
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spelling pubmed-86375632021-12-09 T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma Thanindratarn, Pichaya Wei, Ran Dean, Dylan C. Singh, Arun Federman, Noah Nelson, Scott D. Hornicek, Francis J. Duan, Zhenfeng Mol Oncol Research Articles T‐lymphokine‐activated killer (T‐LAK) cell‐originated protein kinase (TOPK) is an emerging target with critical roles in various cancers; however, its expression and function in osteosarcoma remain unexplored. We evaluated TOPK expression using RNA sequencing and gene expression data from public databases (TARGET‐OS, CCLE, GTEx, and GENT2) and immunohistochemistry in an osteosarcoma tissue microarray (TMA). TOPK gene expression was significantly higher in osteosarcoma than normal tissues and directly correlated with shorter overall survival. TOPK was overexpressed in 83.3% of the osteosarcoma specimens within our TMA and all osteosarcoma cell lines, whereas normal osteoblast cells had no aberrant expression. High expression of TOPK associated with metastasis, disease status, and shorter overall survival. Silencing of TOPK with small interfering RNA (siRNA) decreased cell viability, and inhibition with the selective inhibitor OTS514 suppressed osteosarcoma cell proliferation, migration, colony‐forming ability, and spheroid growth. Enhanced chemotherapeutic sensitivity and a synergistic effect were also observed with the combination of OTS514 and either doxorubicin or cisplatin in osteosarcoma cell lines. Taken together, our study demonstrated that TOPK is a potential prognostic biomarker and therapeutic target for osteosarcoma treatment. John Wiley and Sons Inc. 2021-06-29 2021-12 /pmc/articles/PMC8637563/ /pubmed/34115928 http://dx.doi.org/10.1002/1878-0261.13039 Text en © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Thanindratarn, Pichaya
Wei, Ran
Dean, Dylan C.
Singh, Arun
Federman, Noah
Nelson, Scott D.
Hornicek, Francis J.
Duan, Zhenfeng
T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_full T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_fullStr T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_full_unstemmed T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_short T‐LAK cell‐originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma
title_sort t‐lak cell‐originated protein kinase (topk): an emerging prognostic biomarker and therapeutic target in osteosarcoma
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637563/
https://www.ncbi.nlm.nih.gov/pubmed/34115928
http://dx.doi.org/10.1002/1878-0261.13039
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