title: TIS21(/BTG2/PC3) inhibits interleukin-6 expression via downregulation of STAT3 pathway.
abstract: Cancer cell growth was increased when co-cultured with fibroblasts, however, no effect was observed when co-cultured with TIS21-overexpressed fibroblast. Therefore, the role of TIS21 played in cancer microenvironment was investigated. TIS21 decreased interleukin-6 (IL-6) expression in human dermal fibroblast (HDF). Adenoviral transduction of TIS21 gene to HDF decreased the secretion of IL-6, whereas knockdown of the gene increased IL-6 expression. Furthermore, TIS21 overexpression inhibited STAT3 binding to IL-6 promoter region as well as JAK2-STAT3 signaling by inhibiting reactive oxygen species (ROS) generation by being localized in mitochondria. Mitochondria-target TIS21 (MT-TIS21) also inhibited IL-6 expression by downregulating STAT3 phosphorylation, whereas NF-κB pathway was not influenced by TIS21 expression. These results indicate that TIS21 negatively regulated cancer cell growth by inhibiting IL-6 expression through downregulation of STAT3 activation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University, School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Linh Nguyen
authors.initials: LN
authors.lastname: Quy
authors.forename: Yong Won
authors.initials: YW
authors.lastname: Choi
authors.forename: Yeong Hwa
authors.initials: YH
authors.lastname: Kim
authors.forename: Yong-Joon
authors.initials: YJ
authors.lastname: Chwae
authors.forename: Tae Jun
authors.initials: TJ
authors.lastname: Park
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics*; D053614:Janus Kinase 2 / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017874:Immediate-Early Proteins; D015850:Interleukin-6; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human; D053614:Janus Kinase 2
keywords: Interleukin-6; JAK2; ROS; STAT3; TIS21(/BTG2/PC3)