The involvement of FoxO in cell survival and chemosensitivity mediated by Mirk/Dyrk1B in ovarian cancer
Open Access
- 12 December 2011
- journal article
- Published by Spandidos Publications in International Journal of Oncology
- Vol. 40 (4), 1203-1209
- https://doi.org/10.3892/ijo.2011.1293
Abstract
Minibrain-related kinase (Mirk) is a serine/threonine kinase which is also known as the dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B). It is known that Dyrk1A, the closest family member to Mirk/Dyrk1B can mediate cellular localization of mammalian forkhead subclass O (FoxO1), a transcription factor, although the effect of Mirk/Dyrk1B on FoxO factors remains to be defined. In this study, we showed that Mirk/Dyrk1B protein was overexpressed in 5 of 8 ovarian cancer cell lines and negatively correlated with the protein level of FoxO factors (FoxO1+FoxO3A). Knockdown of Mirk by small interfering RNA (siRNA) resulted in cell apoptosis and sensitized cells to cisplatin accompanied by nuclear translocation of FoxO1 and/or FoxO3A as well as increased Bim, TRADD, cleaved caspase-3 and PARP. Furthermore, combined siRNAs of Mirk with FoxO1 and/or FoxO3A led to fewer apoptotic cells and cisplatin sensitivity compared to Mirk siRNA alone, suggesting that FoxO is involved in Mirk-mediated cell survival and chemosensitivity of ovarian cancer. Taken together, Mirk/Dyrk1B plays an important role in ovarian cancer cell survival through modulating FoxO translocation and may be a novel therapeutic target for ovarian cancer.Keywords
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