HIF-1α activates hypoxia-induced PFKFB4 expression in human bladder cancer cells
HIF-1α activates hypoxia-induced PFKFB4 expression in human bladder cancer cells
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HIF-1α 激活缺氧诱导的人膀胱癌细胞中 PFKFB4 的表达
DOI：
10.1016/j.bbrc.2016.05.026
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发表时间：
2016-07-29
影响因子：
3.1
通讯作者：
Xiao, Jianru
中科院分区：
文献类型：
--
作者：
Zhang, Hao;Lu, Chengyin;Xiao, Jianru
据报道，PFKFB 4通过合成果糖-2，6-二磷酸（F2，6 BP）来调节糖酵解，并且已被证明与大多数恶性肿瘤相关。然而，膀胱癌中PFKFB 4表达增加的潜在机制仍不清楚。本研究表明PFKFB 4在膀胱癌组织中过表达。另外，PFKFB 4在低氧条件下膀胱癌细胞中的表达升高，而在无氧条件下，PFKFB 4的表达仍然很低。此外，我们从PFKFB 4启动子区的5个假定HRE中鉴定了低氧反应元件（HRE）-D，并证明HRE-D在膀胱癌细胞中被HIF-1 α反式激活。通过使用双重免疫荧光共定位分析，我们发现在人膀胱癌标本中HIF-1 α的表达与PFKFB 4的表达相关。总之，我们的研究首次确定了HIF-1 α在PFKFB 4和膀胱癌缺氧之间的联系中的关键作用，这可能被证明是治疗膀胱癌的潜在靶点。(C)2016 Elsevier Inc. All rights reserved.
PFKFB4 is reported to regulate glycolysis by synthesizing fructose-2, 6-bisphosphate (F2,6BP) and has proved to be associated with most malignancies. However, the underlying mechanism for increased PFKFB4 expression in bladder cancer remains unclear. The present study demonstrated that PFKFB4 was overexpressed in bladder cancer tissues. In addition, the expression of PFKFB4 elevated in bladder cancer cells in the hypoxic condition, while in nomoxic condition, the expression of PFKFB4 still very low. Furthermore, we identified the hypoxia-responsive elements (HRE)-D from five putative HREs in the promoter region of PFKFB4 and demonstrated that the HRE-D was transactivated by the HIF-1 alpha in bladder cancer cells. By using the Double-immunofluorescence co-localization assay, we revealed that the HIF-1 alpha expression was associated with PFKFB4 expression in human bladder cancer specimens. Altogether, our study for the first time identified the pivotal role of HIF-1 alpha in the connection between PFKFB4 and hypoxia in bladder cancer, which may prove to be a potential target for the treatment of bladder cancer. (C) 2016 Elsevier Inc. All rights reserved.