title: HIF-1α activates hypoxia-induced PFKFB4 expression in human bladder cancer cells.
abstract: 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-1α in bladder cancer cells. By using the Double-immunofluorescence co-localization assay, we revealed that the HIF-1α expression was associated with PFKFB4 expression in human bladder cancer specimens. Altogether, our study for the first time identified the pivotal role of HIF-1α in the connection between PFKFB4 and hypoxia in bladder cancer, which may prove to be a potential target for the treatment of bladder cancer.
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chengyin
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yingzheng
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: czyyltl@163.com.
authors.forename: Tielong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: daman123456789@163.com.
authors.forename: Tianrui
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: jianruxiao83@163.com.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025481:Phosphofructokinase-2 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C506672:PFKFB4 protein, human; D025481:Phosphofructokinase-2
keywords: Bladder cancer; HIF-1α; HREs; Hypoxia; PFKFB4