Journal Article

The kinase Mirk is a potential therapeutic target in osteosarcoma

Cao Yang, Diana Ji, Edward J. Weinstein, Edwin Choy, Francis J. Hornicek, Kirkham B. Wood, Xianzhe Liu, Henry Mankin and Zhenfeng Duan

in Carcinogenesis

Volume 31, issue 4, pages 552-558
Published in print April 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgp330
The kinase Mirk is a potential therapeutic target in osteosarcoma

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Osteosarcoma is the most common primary malignant bone tumor affecting children and adolescents. The majority of patients are treated by surgery and chemotherapy but have limited alternative therapeutic options. Kinases play an important role in the growth and survival of tumor cells. We aim to identify specific kinases to be vital in the survival of osteosarcoma cells and thus may be a key target in creating novel anticancer therapies. A lentiviral short hairpin RNA kinase library, screened osteosarcoma cells, identified kinase minibrain-related kinase (Mirk) (Dyrk1B) as a potential target. Knockdown Mirk expression could inhibit cell growth and induce apoptosis. Chemically synthetic small interfering RNA knockdown and complementary DNA rescue assay further confirmed the results from the decrease of Mirk gene expression. The relationship between Mirk gene expression and the clinical characteristics of patients with osteosarcoma was investigated using tissue microarray and immunohistochemistry analysis. The data indicate that the overall survival rate of patients with Mirk high staining (high levels of Mirk protein expression) is significantly shorter than those with Mirk low staining and moderate staining. This highlights Mirk’s potential to serve as a promising target for molecular therapy in the treatment of osteosarcoma.

Journal Article.  4619 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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