title: KLF5 promotes hypoxia-induced survival and inhibits apoptosis in non-small cell lung cancer cells via HIF-1α.
abstract: Transcription factor Krüppel-like factors 5 (KLF5) is overexpressed in a wide range of tumor tissues and acts as a prognostic factor in cancer. However, the role of KLF5 in non-small cell lung cancer is not clear. Hypoxia plays a vital part in the development of cancer via hypoxia-inducible factor 1 (HIF-1). Our study showed that hypoxia (1% O2) increased cell viability, clonality and proliferation and inhibited cell apoptosis in A549 cells. The expression of HIF-1α and KLF5 was increased time-dependently in hypoxia. Using small interfering RNA (siRNA) targeting KLF5 or HIF-1α, we demonstrated that KLF5 or HIF-1α knockdown inhibited hypoxia-induced cell survival and promoted cell apoptosis by actively downregulating cyclin B1, survivin and upregulating caspase-3. Given the similar effect of KLF5 and HIF-1α on cell survival, an attempt was made to investigate the putative interaction of them in hypoxia. KLF5 was revealed to co-immunoprecipitate with HIF-1α and hypoxia increased the amount of KLF5 and HIF-1α complex. Moreover, silencing of KLF5 decreased HIF-1α expression while KLF5 was not affected by HIF-1α inhibition in hypoxia, confirming the effect of KLF5 on upregulation of HIF-1α. In conclusion, this study identified hypoxia as a tumor promoter by triggering KLF5 → HIF-1α → cyclin B1/survivin/caspase-3 in lung cancer cells.
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Xiaochen
authors: X
authors: Li
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Xiansheng
authors: X
authors: Liu
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Yongjian
authors: Y
authors: Xu
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Jin
authors: J
authors: Liu
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Min
authors: M
authors: Xie
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Wang
authors: W
authors: Ni
authors: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
authors: Shixin
authors: S
authors: Chen
mesh_terms: D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors