Osteosarcoma is the most common primary bone malignancy, mainly occurring in children and adolescents. Cytoskeleton-associated protein 2 (CKAP2), which plays important roles in cell proliferation, has been reported to be overexpressed in diverse human cancers. In the present study, we aimed at exploring the expression and functions of CKAP2 in osteosarcoma. The mRNA and protein expression of CKAP2 was analyzed on collected osteosarcoma and control bone cyst tissues. The results indicated that CKAP2 expression was remarkably elevated in osteosarcoma tissues compared with bone cysts tissues. The expression level of CKAP2 in osteosarcoma was associated with overall survival, tumor size and tumor stage. In addition, down-regulation of CKAP2 by RNA interference in osteosarcoma cell lines, MG63 and SW1353, caused a remarkable inhibition in cell proliferation in vitro and xenograft growth in nude mice. Silencing of CKAP2 also significantly induced G0/G1 arrest and cell apoptosis of osteosarcoma cells. Furthermore, phosphorylation levels of Janus kinase 2 (JAK2) and Signal transducers and activators of transcription 3 (STAT3) were significantly reduced in CKAP2 knockdown cells. The expression of downstream targets of JAK2/STAT3 signaling, Cyclin D1, Bcl-2 and survivin, was also decreased in CKAP2 knockdown cells. Such aberrations can be rescued by re-expression of RNAi-resistant CKAP2. Collectively, the present study indicates that CKAP2 is a potential oncogene by targeting JAK2/STAT3 signaling, and that CKAP2 may serve as a novel target for osteosarcoma therapy.
Keywords: Apoptosis; CKAP2; JAK2/STAT3; Osteosarcoma.
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