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Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma

Osteosarcoma is the most common primary malignancy of bones and frequently affects young children and adolescents. There are several challenges associated with treating osteosarcoma owing to the aggressiveness of the disease, as well as the risk of chemoresistance. Numerous studies are being perform...

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Autores principales: Jeddo, Salim F.A., Wei, Xianfu, Li, Ka, Li, Xin, Yang, Qiang, Dongol, Samina, Li, Jianmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388486/
https://www.ncbi.nlm.nih.gov/pubmed/32705239
http://dx.doi.org/10.3892/or.2020.7686
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author Jeddo, Salim F.A.
Wei, Xianfu
Li, Ka
Li, Xin
Yang, Qiang
Dongol, Samina
Li, Jianmin
author_facet Jeddo, Salim F.A.
Wei, Xianfu
Li, Ka
Li, Xin
Yang, Qiang
Dongol, Samina
Li, Jianmin
author_sort Jeddo, Salim F.A.
collection PubMed
description Osteosarcoma is the most common primary malignancy of bones and frequently affects young children and adolescents. There are several challenges associated with treating osteosarcoma owing to the aggressiveness of the disease, as well as the risk of chemoresistance. Numerous studies are being performed with the aim of identifying improved prognostic and therapeutic markers for this malignancy. Maternal embryonic leucine zipper kinase (MELK) is an oncogene that has been studied in several types of cancer in recent years. In the present study, the expression of MELK in osteosarcoma and normal tissue samples was examined, and the effects of MELK expression on osteosarcoma cellular proliferation, metastasis, the cell cycle and apoptosis were demonstrated using CCK-8, wound healing, migration and invasion and apoptosis assays. The role of MELK in cancer progression in osteosarcoma was determined, revealing the association between MELK expression and prognosis of osteosarcoma. It was demonstrated that knockdown of MELK resulted in reduced proliferation, migration and invasion in vitro along with potentiation of apoptosis and cell cycle arrest. Furthermore, the effect of the targeted MELK inhibitor, OTSSP167, on tumor progression of osteosarcoma in vitro and in vivo was assessed. Mechanistically, it was demonstrated that MELK promoted osteosarcoma proliferation and metastasis by regulating PCNA and MMP9 expression via the PI3K/Akt/mTOR signaling pathway. Thus, the present study revealed the oncogenic role played by MELK, and established MELK as a valuable prognostic and therapeutic marker in osteosarcoma.
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spelling pubmed-73884862020-08-05 Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma Jeddo, Salim F.A. Wei, Xianfu Li, Ka Li, Xin Yang, Qiang Dongol, Samina Li, Jianmin Oncol Rep Articles Osteosarcoma is the most common primary malignancy of bones and frequently affects young children and adolescents. There are several challenges associated with treating osteosarcoma owing to the aggressiveness of the disease, as well as the risk of chemoresistance. Numerous studies are being performed with the aim of identifying improved prognostic and therapeutic markers for this malignancy. Maternal embryonic leucine zipper kinase (MELK) is an oncogene that has been studied in several types of cancer in recent years. In the present study, the expression of MELK in osteosarcoma and normal tissue samples was examined, and the effects of MELK expression on osteosarcoma cellular proliferation, metastasis, the cell cycle and apoptosis were demonstrated using CCK-8, wound healing, migration and invasion and apoptosis assays. The role of MELK in cancer progression in osteosarcoma was determined, revealing the association between MELK expression and prognosis of osteosarcoma. It was demonstrated that knockdown of MELK resulted in reduced proliferation, migration and invasion in vitro along with potentiation of apoptosis and cell cycle arrest. Furthermore, the effect of the targeted MELK inhibitor, OTSSP167, on tumor progression of osteosarcoma in vitro and in vivo was assessed. Mechanistically, it was demonstrated that MELK promoted osteosarcoma proliferation and metastasis by regulating PCNA and MMP9 expression via the PI3K/Akt/mTOR signaling pathway. Thus, the present study revealed the oncogenic role played by MELK, and established MELK as a valuable prognostic and therapeutic marker in osteosarcoma. D.A. Spandidos 2020-09 2020-07-13 /pmc/articles/PMC7388486/ /pubmed/32705239 http://dx.doi.org/10.3892/or.2020.7686 Text en Copyright: © Jeddo et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Jeddo, Salim F.A.
Wei, Xianfu
Li, Ka
Li, Xin
Yang, Qiang
Dongol, Samina
Li, Jianmin
Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
title Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
title_full Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
title_fullStr Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
title_full_unstemmed Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
title_short Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
title_sort maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388486/
https://www.ncbi.nlm.nih.gov/pubmed/32705239
http://dx.doi.org/10.3892/or.2020.7686
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