title: Tristetraprolin down-regulates IL-23 expression in colon cancer cells.
abstract: Interleukin 23 (IL-23) is an inflammatory cytokine that plays an important role in tumor promotion. Expression of IL-23 is increased in cancer cells and correlates with tumor progression. However, the mechanisms regulating IL-23 expression in cancer cells are still unclear. Here we report that tristetraprolin (TTP), an AU-rich element (ARE)-binding protein, inhibits IL-23 production in CT26 mouse colon cancer cells. Overexpression of TTP decreased the stability of IL-23 mRNA and the expression level of IL-23 in CT26 cells. Conversely, inhibition of TTP by siRNA increased IL-23 production. TTP destabilized a luciferase mRNA reporter containing the IL-23 mRNA 3'UTR, which contains five AREs. Analyses of deletion and point mutants of the IL-23 mRNA 3'UTR demonstrated that the ARE cluster between the third and fifth AREs was responsible for TTP-mediated destabilization of IL-23 mRNA. A RNA electrophoretic mobility shift assay confirmed that TTP binds to this ARE cluster. Taken together, these results demonstrate that TTP acts as a negative regulator of IL-23 gene expression in mouse colon cancer cells and suggest its potential application as a novel therapeutic target to control IL-23-mediated tumor promotion.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea.
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Song Soo
authors.initials: SS
authors.lastname: Yang
authors.forename: Mai-Tram
authors.initials: MT
authors.lastname: Vo
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Cha
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D053759:Interleukin-23 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D017354:Point Mutation; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D053759:Interleukin-23; D012333:RNA, Messenger; D051816:Tristetraprolin; C497552:ZFP36 protein, human; C497553:Zfp36 protein, mouse