Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells
نویسندگان
چکیده
The condensin complex is required for chromosome condensation during mitosis; however, the role of this complex during interphase is unclear. Neuroblastoma is the most common extracranial solid tumor of childhood, and it is often lethal. In human neuroblastoma, MYCN gene amplification is correlated with poor prognosis. This study demonstrates that the gene encoding the condensin complex subunit SMC2 is transcriptionally regulated by MYCN. SMC2 also transcriptionally regulates DNA damage response genes in cooperation with MYCN. Downregulation of SMC2 induced DNA damage and showed a synergistic lethal response in MYCN-amplified/overexpression cells, leading to apoptosis in human neuroblastoma cells. Finally, this study found that patients bearing MYCN-amplified tumors showed improved survival when SMC2 expression was low. These results identify novel functions of SMC2 in DNA damage response, and we propose that SMC2 (or the condensin complex) is a novel molecular target for the treatment of MYCN-amplified neuroblastoma.
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Targeting condensin, a vital spot of MYCN-amplified neuroblastoma
Neuroblastoma is a disease in which malignant cells form in nerve tissue. Amplification of MYCN, a member of the MYC proto-oncogene family, is frequently observed in neuroblastoma, and it is associated with malignant phenotype and poor prognosis.1 in the April 1, 2014 issue of Cell Cycle, Murakami-Tonami et al.2 reported that downregulation of sMC2, a subunit of condensin, leads to cell death t...
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