The involvement of FoxO in cell survival and chemosensitivity mediated by Mirk/Dyrk1B in ovarian cancer.
The involvement of FoxO in cell survival and chemosensitivity mediated by Mirk/Dyrk1B in ovarian cancer.
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FoxO 参与 Mirk/Dyrk1B 介导的卵巢癌细胞存活和化疗敏感性
DOI：
10.3892/ijo.2011.1293
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发表时间：
2012-04
影响因子：
5.2
通讯作者：
Li N
中科院分区：
文献类型：
--
作者：
Gao J;Yang X;Yin P;Hu W;Liao H;Miao Z;Pan C;Li N
迷你脑相关激酶（Mirk）是一种丝氨酸/苏氨酸激酶，也被称为双特异性酪氨酸磷酸化调节激酶1B （Dyrk1B）。已知与Mirk/Dyrk1B最接近的家族成员Dyrk1A可以介导哺乳动物叉头亚类O （FoxO1）的细胞定位，这是一种转录因子，尽管Mirk/Dyrk1B对FoxO因子的影响仍有待确定。在本研究中，我们发现Mirk/Dyrk1B蛋白在8种卵巢癌细胞系中有5种过表达，且与FoxO因子（FoxO1+FoxO3A）蛋白水平呈负相关。小干扰RNA （siRNA）敲低Mirk导致细胞凋亡，顺铂致敏，FoxO1和/或FoxO3A核易位，增加Bim、TRADD、cleaved caspase-3和PARP。此外，与单独Mirk siRNA相比，Mirk siRNA与FoxO1和/或FoxO3A的联合siRNA导致更少的凋亡细胞和顺铂敏感性，这表明FoxO参与了Mirk介导的卵巢癌细胞存活和化疗敏感性。综上所述，Mirk/Dyrk1B通过调节FoxO易位在卵巢癌细胞存活中发挥重要作用，可能成为卵巢癌新的治疗靶点。
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.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.8
作者：
Tang, TTL;Dowbenko, D;Lasky, LA
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Lasky, LA
影响因子：
6.4
作者：
Deng, Rong;Tang, Jun;Zhu, Xiao-Feng
通讯作者：
Zhu, Xiao-Feng
影响因子：
6.4
作者：
Hu, Jing;Nakhla, Hassan;Friedman, Eileen
通讯作者：
Friedman, Eileen
影响因子：
--
作者：
Thompson, FH;Nelson, MA;Taetle, R
通讯作者：
Taetle, R