An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma
An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma
复制标题
DOI：
10.1038/onc.2016.181
复制
发表时间：
2017-01-05
期刊：
影响因子：
8
通讯作者：
Gaubatz, S.
中科院分区：
文献类型：
--
作者：
Iltzsche, F.;Simon, K.;Gaubatz, S.
保守的Myb-MuvB(MMB)多蛋白复合体在有丝分裂基因的转录激活中起着重要作用。MMB靶基因在几种不同的癌症类型中过度表达，它们的高表达与晚期肿瘤状态和不良预后有关。这表明MMB可能通过介导有丝分裂基因的过度表达而促进肿瘤的发生。然而，尽管MMB在生物化学方面已经得到了广泛的表征，但在体内肿瘤发生中对MMB的需求还没有被研究。在这里，我们证明了在致癌K-RAS驱动的小鼠肺癌模型中，MMB是肿瘤形成所必需的。我们还发现了MMB的关键靶基因KIF23在肿瘤发生中对有丝分裂运动的需求。RNA干扰介导的KIF23缺失抑制了体内肺肿瘤的形成，并诱导了肺癌细胞系的凋亡。我们的结果表明，抑制KIF23可能是治疗肺癌的一种策略。
The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate.that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer.