title: The kinase Mirk is a potential therapeutic target in osteosarcoma.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.forename: Diana
authors.initials: D
authors.lastname: Ji
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinstein
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.forename: Kirkham B
authors.initials: KB
authors.lastname: Wood
authors.forename: Xianzhe
authors.initials: X
authors.lastname: Liu
authors.forename: Henry
authors.initials: H
authors.lastname: Mankin
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D017209:Apoptosis; D001859:Bone Neoplasms / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D000097603:Dyrk Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering; D000097603:Dyrk Kinases