The mitochondrial chaperone Prohibitin 1 negatively regulates interleukin-8 in human liver cancers Jin Won Yang1,2*, Ben Murray1*, Lucia Barbier-Torres1*, Ting Liu3, Zhenqiu Liu4, Heping Yang1, Wei Fan1 Jiaohong Wang1, Yuan Li1,3, Ekihiro Seki1, José M. Mato5, and Shelly C. Lu1 From the 1Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, LA, CA 90048, USA; 2College of Pharmacy, Woosuk University, Wanju, South Korea; 3Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China; 4Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA; 5CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Technology, Park of Bizkaia, 48160 Derio, Bizkaia, Spain Running title: Prohibitin 1 negatively regulates IL-8 transcription *Share first-authorship To whom correspondence should be addressed: Shelly C. Lu, M.D., Cedars-Sinai Medical Center, Davis Building, Room #2097, 8700 Beverly Blvd., Los Angeles, CA, 90048. Tel: (310) 423-5692, Fax: (310) 423-0653, e-mail:
[email protected] Keywords: Interleukin-8, Jun N-terminal Kinase, liver cancer, nuclear factor κB, prohibitin 1, tumor supressor ABSTRACT lowered IL-8 expression and secretion. Silencing Prohibitin 1 (PHB1) is a mitochondrial PHB1 increased JNK and NF-κB activity, induced chaperone whose expression is dysregulated in nuclear accumulation of c-JUN and p65 and cancers. In liver cancer, PHB1 acts as a tumor enhanced their binding to the IL-8 promoter suppressor but the mechanisms of tumor containing AP-1 and NF-κB elements. Conditioned suppression are incompletely understood. Here we medium from PHB1-silenced HepG2 cells aimed to determine PHB1 target genes to better increased migration and invasion of parental understand how PHB1 influences liver HepG2 and SK-hep-1 cells, and this was blocked tumorigenesis.