Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma.
Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma.
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DOI：
10.1016/j.canlet.2017.02.013
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发表时间：
2017-05-28
期刊：
影响因子：
9.7
通讯作者：
Ahmad N
中科院分区：
文献类型：
--
作者：
Gutteridge RE;Singh CK;Ndiaye MA;Ahmad N
有限数量的研究表明有丝分裂激酶polo样激酶1（PLK1）和细胞代谢的关联。在这里，采用诱导型RNA干扰的方法在A375黑色素瘤细胞加上PCR阵列和多种验证方法，我们证明了PLK1改变了一些与细胞代谢相关的基因。PLK1敲低导致IDH1、PDP2和PCK1的显著下调和FBP1的上调。免疫途径分析（IPA）确定1）糖酵解和戊糖磷酸途径是与PLK1相关的主要经典途径，2）PLK1抑制调节基因在很大程度上与细胞增殖相关，其中FBP1是关键调节因子。此外，BI 6727介导的PLK1抑制导致体内A375黑色素瘤细胞植入异种移植物中PCK1减少和FBP1增加。此外，PLK1和FBP1之间的负相关性被发现在黑色素瘤细胞中，FBP1的表达显着下调在一组黑色素瘤细胞。此外，BI 6727处理导致A375、Hs294T和G361黑色素瘤细胞中的FBP1上调。总之，我们的研究表明，PLK1可能是黑色素瘤细胞代谢维持的重要调节因子。PLK1基因敲低影响代谢相关基因的调控
A limited number of studies have indicated an association of the mitotic kinase polo-like kinase 1 (PLK1) and cellular metabolism. Here, employing an inducible RNA interference approach in A375 melanoma cells coupled with a PCR array and multiple validation approaches, we demonstrated that PLK1 alters a number of genes associated with cellular metabolism. PLK1 knockdown resulted in a significant downregulation of IDH1, PDP2 and PCK1 and upregulation of FBP1. Ingenuity Pathway Analysis (IPA) identified that 1) glycolysis and the pentose phosphate pathway are major canonical pathways associated with PLK1, and 2) PLK1 inhibition-modulated genes were largely associated with cellular proliferation, with FBP1 being the key modulator. Further, BI 6727-mediated inhibition of PLK1 caused a decrease in PCK1 and increase in FBP1 in A375 melanoma cell implanted xenografts in vivo. Furthermore, an inverse correlation between PLK1 and FBP1 was found in melanoma cells, with FBP1 expression significantly downregulated in a panel of melanoma cells. In addition, BI 6727 treatment resulted in an upregulation in FBP1 in A375, Hs294T and G361 melanoma cells. Overall, our study suggest that PLK1 may be an important regulator of metabolism maintenance in melanoma cells. PLK1 Knockdown Affects Modulation of Metabolism-Related Genes