title: Induction of peroxiredoxin 1 by hypoxia regulates heme oxygenase-1 via NF-κB in oral cancer.
abstract: Overexpression of peroxiredoxin 1 (Prx1) has been observed in numerous cancers including oral squamous cell carcinoma (OSCC). The precise molecular mechanism of up-regulation of Prx1 in carcinogenesis, however, is still poorly understood. The objective of this study is to investigate the relationship between Prx1 and hypoxia, and potential mechanism(s) of Prx1 in OSCC cell line SCC15 and xenograft model. We treated wild-type and Prx1 knockdown SCC15 cells with transient hypoxia followed by reoxygenation. We detected the condition of hypoxia, production of reactive oxygen species (ROS), and expression and/or activity of Prx1, heme oxygenase 1 (HO-1) and nuclear factor-kappa B (NF-κB). We found that hypoxia induces ROS accumulation, up-regulates Prx1, increases NF-κB translocation and DNA binding activity, and down-regulates HO-1 in vitro. In Prx1 knockdown cells, the expression level of HO-1 was increased, while NFκB translocation and DNA binding activity were decreased after hypoxia or hypoxia/reoxygenation treatment. Moreover, we mimicked the dynamic oxygenation tumor microenvironment in xenograft model and assessed the above indices in tumors with the maximal diameter of 2 mm, 5 mm, 10 mm or 15 mm, respectively. Our data showed that tumor hypoxic condition and expression of Prx1 are significantly associated with tumor growth. The expression of HO-1 and NF-κB, and NF-κB DNA binding activity were significantly elevated in 15 mm tumors, and the level of 8-hydroxydeoxyguanosine was increased in 10 mm and 15 mm tumors, compared to those in size of 2 mm. The results from this study provide experimental evidence that overexpression of Prx1 is associated with hypoxia, and Prx1/NF-κB/HO-1 signaling pathway may be involved in oral carcinogenesis.
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hou
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ge
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Miao
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Jing
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Ni
authors.initials: N
authors.lastname: Shi
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Beijing, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Tang
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; C489936:Prrx1 protein, mouse; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D003849:Deoxyguanosine; D010100:Oxygen